Hostname: page-component-78c5997874-t5tsf Total loading time: 0 Render date: 2024-11-17T13:10:42.927Z Has data issue: false hasContentIssue false
  • English
  • Français

Sensitizing effect of early adversity on depressive reactions to later proximal stress: Moderation by polymorphisms in serotonin transporter and corticotropin releasing hormone receptor genes in a 20-year longitudinal study

Published online by Cambridge University Press:  25 November 2014

Lisa R. Starr ,
Constance Hammen ,
Christopher C. Conway ,
Elizabeth Raposa  and
Patricia A. Brennan
Lisa R. Starr*
Affiliation:
University of Rochester
Constance Hammen
Affiliation:
University of California, Los Angeles
Christopher C. Conway
Affiliation:
University of California, Los Angeles
Elizabeth Raposa
Affiliation:
University of California, Los Angeles
Patricia A. Brennan
Affiliation:
Emory University
*
Address correspondence and reprint requests to: Lisa R. Starr, Department of Clinical and Social Sciences in Psychology, University of Rochester, 491 Meliora, Box 270266, Rochester, NY 14627; E-mail: lisa.starr@rochester.edu.
Get access Rights & Permissions [Opens in a new window]

Abstract

Previous research supports gene–environment interactions for polymorphisms in the corticotropin hormone receptor 1 gene (CRHR1) and the serotonin transporter gene linked polymorphic region (5-HTTLPR) in predicting depression, but it has rarely considered genetic influences on stress sensitization processes, whereby early adversities (EA) increase depressive reactivity to proximal stressors later in life. The current study tested a gene–environment–environment interaction (G × E × E; specifically, gene–EA–proximal stress interaction) model of depression in a 20-year longitudinal study. Participants were assessed prospectively for EA up to age 5 and recent chronic stress and depressive symptoms at age 20 and genotyped for CRHR1 single nucleotide polymorphism rs110402 and 5-HTTLPR. EA predicted stronger associations between recent chronic stress and depression, and the effect was moderated by genes. CRHR1 A alleles and 5-HTTLPR short alleles were associated with greater stress sensitization (i.e., greater depressive reactivity to chronic stress for those also exposed to high levels of EA). The results are consistent with the notion that EA exposure results in neurobiological and cognitive–emotional consequences (e.g., altered hypothalamic–pituitary–adrenal axis functioning), leading to emotional distress in the face of recent stressors among those with certain genetic characteristics, although further research is needed to explore explanatory mechanisms.

Type
Regular Articles
Information
Development and Psychopathology , Volume 26 , Special Issue 4pt2: Multilevel Developmental Perspectives Toward Understanding Internalizing Psychopathology: Current Research and Future Directions , November 2014 , pp. 1241 - 1254
Copyright
Copyright © Cambridge University Press 2014 

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

Achenbach, T. M. (2009). The Achenbach System of Empirically Based Assessemnt (ASEBA): Development, findings, theory, and applications. Burlington, VT: University of Vermont, Research Center for Children, Youth and Families.Google Scholar
Andersen, S. L., Tomada, A., Vincow, E. S., Valente, E., Polcari, A. R., & Teicher, M. H. (2008). Preliminary evidence for sensitive periods in the effect of childhood sexual abuse on regional brain development. Journal of Neuropsychiatry and Clinical Neurosciences, 20, 292–301.Google Scholar
Beck, A. T., Steer, R. A., & Brown, G. K. (1996). The Beck Depression Inventory (2nd ed.). San Antonio, TX: Psychological Corporation.Google Scholar
Beck, A. T., Steer, R. A., & Garbin, M. G. (1988). Psychometric properties of the Beck Depression Inventory: Twenty-five years of evaluation. Clinical Psychology Review, 8, 77–100.Google Scholar
Bedford, A., & Foulds, G. (1978). Delusions–Symptoms–States Inventory of Anxiety and Depression. Windsor: NFER.Google Scholar
Belsky, J., & Pluess, M. (2009). Beyond diathesis stress: Differential susceptibility to environmental influences. Psychological Bulletin, 135, 885.Google Scholar
Bernstein, D., & Fink, L. A. (1998). Childhood Trauma Questionnaire manual. San Antonio, TX: Psychological Corporation.Google Scholar
Bowlby, J. (1980). Attachment and loss. New York: Basic Books.Google Scholar
Bradley, R. G., Binder, E. B., Epstein, M. P., Tang, Y., Nair, H. P., Liu, W., et al. (2008). Influence of child abuse on adult depression: Moderation by the corticotropin-releasing hormone receptor gene. Archives of General Psychiatry, 65, 190.Google Scholar
Brown, G. W., & Harris, T. O. (2008). Depression and the serotonin transporter 5-HRRLPR polymorphism: A review and a hypothesis concerning gene–environment interaction. Journal of Affective Disorders, 111, 1–12.Google Scholar
Carpenter, L. L., Tyrka, A. R., McDougle, C. J., Malison, R. T., Owens, M. J., Nemeroff, C. B., et al. (2004). Cerebrospinal fluid corticotropin-releasing factor and perceived early-life stress in depressed patients and healthy control subjects. Neuropsychopharmacology, 29, 777–784.Google Scholar
Carpenter, L. L., Tyrka, A. R., Ross, N. S., Khoury, L., Anderson, G. M., & Price, L. H. (2009). Effect of childhood emotional abuse and age on cortisol responsivity in adulthood. Biological Psychiatry, 66, 69–75. doi:http://dx.doi.org/10.1016/j.biopsych.2009.02.030 Google Scholar
Caspi, A., Hariri, A. R., Holmes, A., Uher, R., & Moffitt, T. E. (2010). Genetic sensitivity to the environment: The case of the serotonin transporter gene and its implications for studying complex diseases and traits. American Journal of Psychiatry, 167, 509–527.Google Scholar
Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W., Harrington, H., et al. (2003). Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene. Science, 301, 386–389.Google Scholar
Cicchetti, D. (2013). Annual research review: Resilient functioning in maltreated children—Past, present, and future perspectives. Journal of Child Psychology and Psychiatry, 54, 402–422.CrossRefGoogle ScholarPubMed
Cicchetti, D., & Dawson, G. (2002). Editorial: Multiple levels of analysis. Development and Psychopathology, 14, 417–420.Google Scholar
Cicchetti, D., & Rogosch, F. A. (2001). The impact of child maltreatment and psychopathology on neuroendocrine functioning. Development and Psychopathology, 13, 783–804.Google Scholar
Cicchetti, D., Rogosch, F. A., & Oshri, A. (2011). Interactive effects of corticotropin releasing hormone receptor 1, serotonin transporter linked polymorphic region, and child maltreatment on diurnal cortisol regulation and internalizing symptomatology. Development and Psychopathology, 23, 1125.Google Scholar
Cicchetti, D., & Toth, S. L. (2009). The past achievements and future promises of developmental psychopathology: The coming of age of a discipline. Journal of Child Psychology and Psychiatry, 50, 16–25. doi:10.1111/j.1469-7610.2008.01979.x Google Scholar
Cole, S. W., Arevalo, J. M., Takahashi, R., Sloan, E. K., Lutgendorf, S. K., Sood, A. K., et al. (2010). Computational identification of gene-social environment interaction at the human IL6 locus. Proceedings of the National Academy of Sciences, 107, 5681–5686. doi:10.1073/pnas.0911515107 Google Scholar
Comasco, E., Aslund, C., Oreland, L., & Nilsson, K. W. (2013). Three-way interaction effect of 5-HTTLPR, BDNF Val66Met, and childhood adversity on depression: A replication study. European Neuropsychopharmacology. Advance online publication. doi:10.1016/j.euroneuro.2013.01.010 Google Scholar
DeYoung, C. G., Cicchetti, D., & Rogosch, F. A. (2011). Moderation of the association between childhood maltreatment and neuroticism by the corticotropin-releasing hormone receptor 1 gene. Journal of Child Psychology and Psychiatry, 52, 898–906.Google Scholar
Du, L., Bakish, D., & Hrdina, P. D. (2000). Gender differences in association between serotonin transporter gene polymorphism and personality traits. Psychiatric Genetics, 10, 159.Google Scholar
Dunn, E. C., McLaughlin, K. A., Slopen, N., Rosand, J., & Smoller, J. W. (2013). Developmental timing of child maltreatment and symptoms of depression and suicidal ideation in young adulthood: Results from the National Longitudinal Study of Adolescent Health. Depression and Anxiety. doi:10.1002/da.22102 Google Scholar
First, M. B., Spitzer, R. L., Gibbon, M., & Williams, J. B. W. (1995). Structured Clinical Interview for DSM-IV Axis I disorders. Washington, DC: American Psychiatric Press.Google Scholar
Fisher, P. A., Gunnar, M. R., Chamberlain, P., & Reid, J. B. (2000). Preventive intervention for maltreated preschool children: Impact on children's behavior, neuroendocrine activity, and foster parent functioning. Journal of the American Academy of Child & Adolescent Psychiatry, 39, 1356–1364. doi:http://dx.doi.org/10.1097/00004583-200011000-00009 CrossRefGoogle ScholarPubMed
Gillespie, C. F., Phifer, J., Bradley, B., & Ressler, K. J. (2009). Risk and resilience: Genetic and environmental influences on development of the stress response. Depression and Anxiety, 26, 984–992.CrossRefGoogle ScholarPubMed
Gonzalez, A., Jenkins, J. M., Steiner, M., & Fleming, A. S. (2009). The relation between early life adversity, cortisol awakening response and diurnal salivary cortisol levels in postpartum women. Psychoneuroendocrinology, 34, 76–86.Google Scholar
Gotlib, I. H., & Colich, N. L. (in press). Children of depressed parents. In Gotlib, I. & Hammen, C. (Eds.), Handbook of depression (3rd ed.). New York: Guilford Press.Google Scholar
Gotlib, I. H., Joormann, J., Minor, K. L., & Hallmayer, J. (2008). HPA axis reactivity: A mechanism underlying the associations among 5-HTTLPR, stress, and depression. Biological Psychiatry, 63, 847–851.Google Scholar
Grabe, H. J., Schwahn, C., Mahler, J., Schulz, A., Spitzer, C., Fenske, K., et al. (2012). Moderation of adult depression by the serotonin transporter promoter variant (5-HTTLPR), childhood abuse and adult traumatic events in a general population sample. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 159B, 298–309.Google Scholar
Gunnar, M., & Quevedo, K. (2007). The neurobiology of stress and development. Annual Review of Psychology, 58, 145–173.Google Scholar
Gunnar, M. R., & van Dulmen, M. H. M. (2007). Behavior problems in postinstitutionalized internationally adopted children. Development and Psychopathology, 19, 129–148.Google Scholar
Hammen, C., Adrian, C., Gordon, D., Burge, D., Jaenicke, C., & Hiroto, D. (1987). Children of depressed mothers: Maternal strain and symptom predictors of dysfunction. Journal of Abnormal Psychology, 96, 190–198.Google Scholar
Hammen, C., & Brennan, P. (2001). Depressed adolescents of depressed and nondepressed mothers: Tests of an interpersonal impairment hypothesis. Journal of Consulting and Clinical Psychology, 69, 284–294.CrossRefGoogle ScholarPubMed
Hammen, C., Brennan, P., & Keenan-Miller, D. (2008). Patterns of adolescent depression to age 20: The role of maternal depression and youth interpersonal dysfunction. Journal of Abnormal Child Psychology, 36, 1189–1198.Google Scholar
Hammen, C., Brennan, P., Keenan-Miller, D., Hazel, N., & Najman, J. (2010). Chronic and acute stress, gender, and serotonin transporter gene–environment interactions predicting depression in youth. Journal of Child Psychiatry and Psychology, 51, 180–187.CrossRefGoogle Scholar
Hammen, C., Hazel, N., Brennan, P., & Najman, J. (2012). Intergenerational transmission and continuity of stress and depression: Depressed women and their offspring in 20 years of follow-up. Psychological Medicine, 42, 931–942.Google Scholar
Hammen, C., Henry, R., & Daley, S. (2000). Depression and sensitization to stressors among young women as a function of childhood adversity. Journal of Consulting and Clinical Psychology, 68, 782–787.CrossRefGoogle ScholarPubMed
Hammen, C., Rudolph, K. R., & Abaied, J. (in press). Child and adolescent depression. In Mash, E. J. & Barkley, R. A. (Eds.), Child psychopathology (3rd ed.). New York: Guilford Press.Google Scholar
Harkness, K. L., Bruce, A. E., & Lumley, M. N. (2006). The role of childhood abuse and neglect in the sensitization to stressful life events in adolescent depression. Journal of Abnormal Psychology, 115, 730–741.Google Scholar
Hayes, A. F. (2013). Introduction to mediation, moderation, and conditional process analysis: A regression-based approach. New York: Guilford Press.Google Scholar
Hazel, N., Hammen, C., Brennan, P., & Najman, J. (2008). Early childhood adversity and adolescent depression: Mediating role of continued stress. Psychological Medicine, 38, 581–589.Google Scholar
Heim, C., & Binder, E. B. (2012). Current research trends in early life stress and depression: Review of human studies on sensitive periods, gene–environment interactions, and epigenetics. Experimental Neurology, 233, 102–111. doi:http://dx.doi.org/10.1016/j.expneurol.2011.10.032 Google Scholar
Heim, C., Bradley, B., Mletzko, T. C., Deveau, T. C., Musselman, D. L., Nemeroff, C. B., et al. (2009). Effect of childhood trauma on adult depression and neuroendocrine function: Sex-specific moderation by CRH receptor 1 gene. Frontiers in Behavioral Neuroscience, 3, 41.Google Scholar
Heim, C., & Nemeroff, C. B. (2001). The role of childhood trauma in the neurobiology of mood and anxiety disorders: Preclinical and clinical studies. Biological Psychiatry, 49, 1023–1039.Google Scholar
Heim, C., Newport, D. J., Mletzko, T., Miller, A. H., & Nemeroff, C. B. (2008). The link between childhood trauma and depression: Insights from HPA axis studies in humans. Psychoneuroendocrinology, 33, 693–710.Google Scholar
Homberg, J. R., & van den Hove, D. L. A. (2012). The serotonin transporter gene and functional and pathological adaptation to environmental variation across the life span. Progress in Neurobiology, 99, 117–127.CrossRefGoogle ScholarPubMed
Hsu, D. T., Mickey, B. J., Langenecker, S. A., Heitzeg, M. M., Love, T. M., Wang, H., et al. (2012). Variation in the corticotropin-releasing hormone receptor 1 (CRHR1) gene influences fMRI signal responses during emotional stimulus processing. Journal of Neuroscience, 32, 3253–3260.Google Scholar
Institute of Medicine and National Research Council. (2013). New directions in child abuse and neglect research. Washington, DC: National Academies Press.Google Scholar
Ishitobi, Y., Nakayama, S., Yamaguchi, K., Kanehisa, M., Higuma, H., Maruyama, Y., et al. (2012). Association of CRHR1 and CRHR2 with major depressive disorder and panic disorder in a Japanese population. American Journal of Medical Genetics 159B, 429–436.Google Scholar
Karg, K., Burmeister, M., Shedden, K., & Sen, S. (2011). The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited: Evidence of genetic moderation. Archives of General Psychiatry, 68, 444–454.Google Scholar
Keeping, J. D., Najman, J. M., Morrison, J., Western, J. S., Andersen, M. J., & Williams, G. M. (1989). A prospective longitudinal study of social, psychological, and obstetrical factors in pregnancy: Response rates and demographic characteristics of the 8,556 respondents. British Journal of Obstetrics and Gynecology, 96, 289–297.Google Scholar
Keiley, M. K., Howe, T. R., Dodge, K. A., Bates, J. E., & Pettit, G. S. (2001). The timing of child physical maltreatment: A cross-domain growth analysis of impact on adolescent externalizing and internalizing problems. Development and Psychopathology, 13, 891–912.Google Scholar
Kendler, K., & Baker, J. (2007). Genetic influences on measures of the environment. Psychological Medicine, 37, 615–626.Google Scholar
Kessler, R. C., Davis, C. G., & Kendler, K. S. (1997). Childhood adversity and adult psychiatric disorder in the U.S. National Comorbidity Survey. Psychological Medicine, 27, 1101–1119.Google Scholar
Kessler, R. C., & Magee, W. J. (1993). Childhood adversities and adult depression: Basic patterns of association in a US national survey. Psychological Medicine, 23, 679–690.Google Scholar
Kessler, R. C., McGonagle, K. A., Swartz, M., Blazer, D. G., & Nelson, C. B. (1993). Sex and depression in the National Comorbidity Survey: I. Lifetime prevalence, chronicity, and recurrence. Journal of Affective Disorders, 29, 85–96.Google Scholar
Kessler, R., McLaughlin, K., Green, J., Gruber, M., Sampson, N., Zaslavsky, A., et al. (2010). Childhood adversities and adult psychopathology in the WHO World Mental Health Surveys. British Journal of Psychiatry, 197, 378–385.Google Scholar
Lasa, L., Ayuso-Mateos, J. L., Vazquez-Barquero, J. L., Diez-Manrique, F. J., & Dowrick, C. F. (2000). The use of the Beck Depression Inventory to screen for depression in the general population: A preliminary analysis. Journal of Affective Disorders, 57, 261–265.Google Scholar
Lewis, G., Collishaw, S., Harold, G., Rice, F., & Thapar, A. (2012). Maternal depression and child and adolescent depression symptoms: An exploratory test for moderation by CRHR1, FKBP5 and NR3C1 gene variants. Behavior Genetics, 42, 121–132.Google Scholar
Mandelli, L., Serretti, A., Marino, E., Pirovano, A., Calati, R., & Colombo, C. (2007). Interaction between serotonin transporter gene, catechol-O-methyltransferase gene and stressful life events in mood disorders. International Journal of Neuropsychopharmacology, 10, 437–447.Google Scholar
Masten, A. (2007). Resilience in developing systems: Progress and promise as the fourth waves rises. Development and Psychopathology, 19, 921–930.Google Scholar
McLaughlin, K., Conron, K., Koenen, K., & Gilman, S. (2010). Childhood adversity, adult stressful life events, and risk of past year psychiatric disorder: A test of the stress sensitization hypothesis in a population-based sample of adults. Psychological Medicine, 40, 1647–1658.Google Scholar
McLaughlin, K., Green, J., Gruber, M., Sampson, N., Zaslovsky, A., & Kessler, R. (2012). Childhood adversities and first onset of psychiatric disorders in a national sample of US adolescents. Archives of General Psychiatry, 69, 1151–1160.Google Scholar
Moffitt, T., Caspi, A., & Rutter, M. (2005). Strategy for investigating interactions between measured genes and measured environments. Archives of General Psychiatry, 62, 473–481.Google Scholar
Monroe, S. M., & Reid, M. W. (2008). Gene–environment interactions in depression research: Genetic polymorphisms and life-stress polyprocedures. Psychological Science, 19, 947–956.Google Scholar
Munafò, M. R., Brown, S. M., & Hariri, A. R. (2008). Serotonin transporter (5-HTTLPR) genotype and amygdala activation: A meta-analysis. Biological Psychiatry, 63, 852–857.Google Scholar
National Research Council. (2009). Preventing mental, emotional, and behavioral disorders among young people: Progress and possibilities. Washington, DC: National Academies Press.Google Scholar
Papiol, S., Arias, B., Gastó, C., Gutiárrez, B., Catalán, R., & Fañanás, L. (2007). Genetic variability at HPA axis in major depression and clinical response to antidepressant treatment. Journal of Affective Disorders, 104, 83–90.Google Scholar
Pariante, C. M., & Lightman, S. L. (2008). The HPA axis in major depression: Classical theories and new developments. Trends in Neurosciences, 31, 464–468.Google Scholar
Pergamin-Hight, L., Bakermans-Kranenburg, M. J., van IJzendoorn, M. H., & Bar-Haim, Y. (2012). Variations in the promoter region of the serotonin transporter gene and biased attention for emotional information: A meta-analysis. Biological Psychiatry, 71, 373–379.Google Scholar
Polanczyk, G., Caspi, A., Williams, B., Price, T. S., Danese, A., Sugden, K., et al. (2009). Protective effect of CRHR1 gene variants on the development of adult depression following childhood maltreatment: Replication and extension. Archives of General Psychiatry, 66, 978–985.Google Scholar
Posener, J. A., DeBattista, C., Williams, G. H., Chmura Kraemer, H., Kalehzan, B. M., & Schatzberg, A. F. (2000). 24-h monitoring of cortisol and corticotropin secretion in psychotic and nonpsychotic major depression. Archives of General Psychiatry, 57, 755–760.Google Scholar
Ray, L., Sehl, M., Bujarski, S., Hutchison, K., Blaine, S., & Enoch, M. A. (2013). The CRHR1 gene, trauma exposure, and alcoholism risk: A test of G × E effects. Genes, Brain, and Behavior, 12, 361–369.Google Scholar
Ressler, K., Bradley, B., Mercer, K., Deveau, T., Smith, A., Gillespie, C., et al. (2010). Polymorphisms in CRHR1 and the serotonin transporter loci: Gene × Gene × Environment interactions on depressive symptoms. American Journal of Medical Genetics, 153B, 812–824.Google Scholar
Risch, N., Herrell, R., Lehner, T., Liang, K.-Y., Eaves, L., Hoh, J., et al. (2009). Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression. Journal of the American Medical Association, 301, 2462–2471.Google Scholar
Rogeness, G. A., & McClure, E. B. (1996). Development and neurotransmitter–environmental interactions. Development and Psychopathology, 8, 183–199.Google Scholar
Rutter, M. (2005). Environmentally mediated risks for psychopathology: Research strategies and findings. Journal of the American Academy of Child & Adolescent Psychiatry, 44, 3–18.Google Scholar
Spanier, G. B. (1976). Measuring dyadic adjustment: New scales for assessing the quality of marriage and similar dyads. Journal of Marriage and the Family, 38, 15–28.Google Scholar
Starr, L. R., Hammen, C., Brennan, P. A., & Najman, J. M. (2012). Serotonin transporter gene as a predictor of stress generation in depression. Journal of Abnormal Psychology, 4, 810–818.Google Scholar
Taylor, S. E., Karlamangla, A. S., Friedman, E. M., & Seeman, T. E. (2011). Early environment affects neuroendocrine regulation in adulthood. Social Cognitive and Affective Neuroscience, 6, 244–251.Google Scholar
Toth, S. L., & Manly, J. T. (2011). Bridging research and practice: Challenges and successes in implementing evidence-based preventive intervention strategies for child maltreatment. Child Abuse and Neglect, 35, 633–636. doi:http://dx.doi.org/10.1016/j.chiabu.2011.05.003 Google Scholar
Toth, S. L., Rogosch, F. A., Manly, J. T., & Cicchetti, D. (2006). The efficacy of toddler–parent psychotherapy to reorganize attachment in the young offspring of mothers with major depressive disorder: A randomized preventive trial (Vol. 74, pp. 1006–1016). Washington, DC: American Psychological Association.Google Scholar
Uher, R., & McGuffin, P. (2010). The moderation by the serotonin transporter gene of environmental adversity in the etiology of depression: 2009 update. Molecular Psychiatry, 15, 18–22.Google Scholar
van IJzendoorn, M. H., Schuengel, C., & Bakermans-Kranenburg, M. J. (1999). Disorganized attachment in early childhood: Meta-analysis of precursors, concomitants, and sequelae. Development and Psychopathology, 11, 225–249.Google Scholar
Wasserman, D., Wasserman, J., Rozanov, V., & Sokolowski, M. (2009). Depression in suicidal males: Genetic risk variants in the CRHR1 gene. Genes, Brain and Behavior, 8, 72–79.CrossRefGoogle ScholarPubMed
Wasserman, D., Wasserman, J., & Sokolowski, M. (2010). Genetics of HPA-axis, depression and suicidality. European Psychiatry, 25, 278–280.Google Scholar
Way, B., & Taylor, S. E. (2010). Social influences on health: Is serotonin a critical mediator? Psychosomatic Medicine, 72, 107–112.Google Scholar
Wendland, J. R., Martin, B. J., Kruse, M. R., Lesch, K. P., & Murphy, D. L. (2006). Simultaneous genotyping of four functional loci of human SLC6A4, with a reappraisal of 5-HTTLPR and rs25531. Molecular Psychiatry, 11, 224–226.Google Scholar
Wismer Fries, A. B., Shirtcliff, E. A., & Pollak, S. D. (2008). Neuroendocrine dysregulation following early social deprivation in children. Developmental Psychobiology, 50, 588–599.Google Scholar