Psychoneuroimmunology of Early-Life Stress: The Hidden Wounds of Childhood Trauma

Neuropsychopharmacology

Volumn 42, Issue 1, 2017, Pages 99-114

  Danese, Andrea ^a,b   J Lewis, Stephanie ^a  

^a KING'S COLLEGE LONDON   (United Kingdom)

^b SOUTH LONDON AND MAUDSLEY NHS FOUNDATION TRUST   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ADAPTIVE IMMUNITY; BRAIN DEVELOPMENT; BRAIN FUNCTION; CHILDHOOD TRAUMA; CLINICAL OUTCOME; EARLY LIFE STRESS; EXPERIENCE; HUMAN; IMMUNE SYSTEM; IMMUNOSTIMULATION; INFLAMMATION; INJURY; MENTAL DISEASE; MENTAL PATIENT; NONHUMAN; PRIORITY JOURNAL; PSYCHOPHYSIOLOGY; REVIEW; TREATMENT RESPONSE; ANIMAL; BRAIN; CHILDHOOD TRAUMA SURVIVOR; GROWTH, DEVELOPMENT AND AGING; IMMUNOLOGY; MENTAL STRESS; PSYCHONEUROIMMUNOLOGY;

ADULT SURVIVORS OF CHILD ADVERSE EVENTS; ANIMALS; BRAIN; HUMANS; INFLAMMATION; MENTAL DISORDERS; PSYCHONEUROIMMUNOLOGY; STRESS, PSYCHOLOGICAL;

EID: 84991687543     PISSN: 0893133X     EISSN: 1740634X     Source Type: Journal    
DOI: 10.1038/npp.2016.198     Document Type: Review

References (209)

1. Ader R (1983). Developmental psychoneuroimmunology. Dev Psychobiol 16:251-267.
2. Ader R, Friedman SB (1965). Differential early experiences and susceptibility totransplanted tumor in the rat. J Comp Physiol Psychol 59: 361-364.
3. Agnew-Blais J, Danese A (2016). Childhood maltreatment and unfavourable clinicaloutcomes in bipolar disorder: a systematic review and meta-analysis. LancetPsychiatry 3: 342-349.
4. Anda RF, Croft JB, Felitti VJ, Nordenberg D, Giles WH, Williamson DF, et al. (1999). Adverse childhood experiences and smoking during adolescence and adulthood. JAMA 282: 1652-1658.
5. Avitsur R, Hunzeker J, Sheridan JF (2006). Role of early stress in the individualdifferences in host response to viral infection. Brain Behav Immun 20: 339-348.
6. Bailey MT, Coe CL (1999). Maternal separation disrupts the integrity of the intestinalmicroflora in infant rhesus monkeys. Dev Psychobiol 35: 146-155.
7. Balleine BW, Delgado MR, Hikosaka O (2007). The role of the dorsal striatum inreward and decision-making. J Neurosci 27: 8161-8165.
8. Barnes PJ, Adcock IM (2009). Glucocorticoid resistance in inflammatory diseases. Lancet 373: 1905-1917.
9. Bateson P, Barker D, Clutton-Brock T, Deb D, D'Udine B, Foley RA, et al. (2004). Developmental plasticity and human health. Nature 430: 419-421.
10. Baumeister D, Akhtar R, Ciufolini S, Pariante CM, Mondelli V (2015). Childhoodtrauma and adulthood inflammation: a meta-analysis of peripheral C-reactiveprotein, interleukin-6 and tumour necrosis factor-. Mol Psychiatry 21: 642-649.
11. Beattie EC, Stellwagen D, Morishita W, Bresnahan JC, Ha BK, Zastrow Von M, et al. (2002). Control of synaptic strength by glial TNFalpha. Science 295: 2282-2285.
12. Berk M, Kapczinski F, Andreazza AC, Dean OM, Giorlando F, Maes M, et al. (2011). Pathways underlying neuroprogression in bipolar disorder: focus on inflammation,oxidative stress and neurotrophic factors. Neurosci Biobehav Rev 35: 804-817.
13. Besedovsky H, del Rey A, Sorkin E, Dinarello CA (1986). Immunoregulatoryfeedback between interleukin-1 and glucocorticoid hormones. Science 233:652-654.
14. Bierhaus A, Wolf J, Andrassy M, Rohleder N, Humpert PM, Petrov D, et al. (2003). A mechanism converting psychosocial stress into mononuclear cell activation. Proc Natl Acad Sci 100: 1920-1925.
15. Bilbo SD, Schwarz JM (2009). Early-life programming of later-life brain and behavior:a critical role for the immune system. Front Behav Neurosci 3: 14.
16. Black DS, Slavich GM (2016). Mindfulness meditation and the immune system:a systematic review of randomized controlled trials. Ann NY Acad Sci 1373:13-24.
17. Bloomfield PS, Selvaraj S, Veronese M, Rizzo G, Bertoldo A, Owen DR, et al. (2016). Microglial activity in people at ultra high risk of psychosis and in schizophrenia: an[11c]pbr28 pet brain imaging study. Am J Psychiatry 173: 44-52.
18. Boulanger LM (2009). Immune proteins in brain development and synaptic plasticity. Neuron 64: 93-109.
19. Breder CD, Hazuka C, Ghayur T, Klug C, Huginin M, Yasuda K, et al. (1994). Regionalinduction of tumor necrosis factor alpha expression in the mouse brainafter systemic lipopolysaccharide administration. Proc Natl Acad Sci 91:11393-11397.
20. Brenhouse HC, Andersen SL (2011a). Developmental trajectories during adolescencein males and females: a cross-species understanding of underlying brainchanges. Neurosci Biobehav Rev 35: 1687-1703.
21. Brenhouse HC, Andersen SL (2011b). Nonsteroidal anti-inflammatory treatmentprevents delayed effects of early life stress in rats. Biol Psychiatry 70: 434-440.
22. Brenhouse HC, Thompson V (2015). Maternal separation increases IBA-1expression: a microglia activation marker in the prefrontal cortex of adolescentmales following a second hit of stress (abstract). Soc Biol Psychiatry.
23. Capuron L, Pagnoni G, Drake DF, Woolwine BJ, Spivey JR, Crowe RJ, et al. (2012). Dopaminergic mechanisms of reduced basal ganglia responses to hedonicreward during interferon alfa administration. Arch Gen Psychiatry 69: 1044-1053.
24. Carpenter LL, Gawuga CE, Tyrka AR, Lee JK, Anderson GM, Price LH (2010). Association between plasma IL-6 response to acute stress and early-life adversityin healthy adults. Neuropsychopharmacology 35: 2617-2623.
25. Casey BJ, Jones RM, Hare TA (2008). The adolescent brain. Ann NY Acad Sci 1124:111-126.
26. Caspi A, Houts RM, Belsky DW, Goldman-Mellor SJ, Harrington H, Israel S, et al. (2014). The p factor: one general psychopathology factor in the structure ofpsychiatric disorders Clin Psychol Sci 2: 119-137.
27. Chalasani SH, Sabelko KA, Sunshine MJ, Littman DR, Raper JA (2003). Achemokine, SDF-1, reduces the effectiveness of multiple axonal repellents and isrequired for normal axon pathfinding. J Neurosci 23: 1360-1371.
28. Chocyk A, Dudys D, Przyborowska A, Majcher I, Makowiak M, Wdzony K (2011). Maternal separation affects the number, proliferation and apoptosis of glia cellsin the substantia nigra and ventral tegmental area of juvenile rats. Neuroscience173: 1-18.
29. Chugani HT, Phelps ME, Mazziotta JC (1987). Positron emission tomography studyof human brain functional development. Ann Neurol 22: 487-497.
30. Cicchetti D, Handley ED, Rogosch FA (2015). Child maltreatment, inflammation,and internalizing symptoms: Investigating the roles of C-reactive protein, genevariation, and neuroendocrine regulation. Dev Psychopathol 27: 553-566.
31. Clancy B, Finlay BL, Darlington RB, Anand KJS (2007). Extrapolating brain developmentfrom experimental species to humans. Neurotoxicology 28: 931-937.
32. Coe C (1996). Developmental psychoneuroimmunology revisited. Brain BehavImmun 10: 185-187.
33. Coe CL, Rosenberg LT, Levine S (1988). Prolonged effect of psychologicaldisturbance on macrophage chemiluminescence in the squirrel monkey. BrainBehav Immun 2: 151-160.
34. Coelho R, Viola TW, Walss-Bass C, Brietzke E, Grassi-Oliveira R (2014). Childhoodmaltreatment and inflammatory markers: a systematic review. Acta PsychiatrScand 129: 180-192.
35. Cohen H, Ziv Y, Cardon M, Kaplan Z, Matar MA, Gidron Y, et al. (2006). Maladaptationto mental stress mitigated by the adaptive immune system via depletion ofnaturally occurring regulatory CD4+CD25+ cells. J Neurobiol 66: 552-563.
36. Cohen S, Janicki-Deverts D, Doyle WJ, Miller GE, Frank E, Rabin BS, et al. (2012). Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk. Proc Natl Acad Sci USA 109: 5995-5999.
37. Cole SW, Conti G, Arevalo JMG, Ruggiero AM, Heckman JJ, Suomi SJ (2012). Transcriptional modulation of the developing immune system by early life socialadversity. Proc Natl Acad Sci USA 109: 20578-20583.
38. Crews FT, Bechara R, Brown LA, Guidot DM, Mandrekar P, Oak S, et al. (2006). Cytokines and alcohol. Alcohol Clin Exp Res 30: 720-730.
39. Crone EA, Dahl RE (2012). Understanding adolescence as a period of socialaffectiveengagement and goal flexibility. Nat Rev Neurosci 13: 636-650.
40. Cryan JF, Dinan TG (2012). Mind-altering microorganisms: the impact of the gutmicrobiota on brain and behaviour. Nat Rev Neurosci 13: 701-712.
41. Danese A (2014). Developmental psychoneuroimmunology: from bench to bedside. Brain Behav Immun 36: 27-28.
42. Danese A, Caspi A, Williams B, Ambler A, Sugden K, Mika J, et al. (2011). Biologicalembedding of stress through inflammation processes in childhood. Mol Psychiatry 16: 244-246.
43. Danese A, Dove R, Belsky DW, Henchy J, Williams B, Ambler A, et al. (2014). Leptindeficiency in maltreated children. Transl Psychiatry 4: e446.
44. Danese A, McCrory E (2015). Child maltreatment. In: Rutter's Child, AdolescentPsychiatry. Wiley Blackwell.
45. Danese A, McEwen BS (2012). Adverse childhood experiences, allostasis, allostaticload, and age-related disease. Physiol Behav 106: 29-39.
46. Danese A, Moffitt TE, Pariante CM, Ambler A, Poulton R, Caspi A (2008). Elevatedinflammation levels in depressed adults with a history of childhood maltreatment. Arch Gen Psychiatry 65: 409-415.
47. Danese A, Pariante CM, Caspi A, Taylor A, Poulton R (2007). Childhoodmaltreatment predicts adult inflammation in a life-course study. Proc Natl AcadSci USA 104: 1319-1324.
48. Danese A, Tan M (2014). Childhood maltreatment and obesity: systematic reviewand meta-analysis. Mol Psychiatry 19: 544-554.
49. Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelley KW (2008). Frominflammation to sickness and depression: when the immune system subjugatesthe brain. Nat Rev Neurosci 9: 46-56.
50. Dargél AA, Godin O, Kapczinski F, Kupfer DJ, Leboyer M (2015). C-reactive proteinalterations in bipolar disorder: a meta-analysis. J Clin Psychiatry 76: 142-150.
51. Delves PJ, Roitt IM (2000a). The immune system. First of two parts. N Engl J Med343: 37-49.
52. Delves PJ, Roitt IM (2000b). The immune system. Second of two parts. N Engl JMed 343: 108-117.
53. Deverman BE, Patterson PH (2009). Cytokines and CNS development. Neuron 64:61-78.
54. Dhabhar FS, McEwen BS (1997). Acute stress enhances while chronic stresssuppresses cell-mediated immunity in vivo: a potential role for leukocytetrafficking. Brain Behav Immun 11: 286-306.
55. Dowling DJ, Levy O (2014). Ontogeny of early life immunity. Trends Immunol 35:299-310.
56. Dube SR, Felitti VJ, Dong M, Chapman DP, Giles WH, Anda RF (2003). Childhoodabuse, neglect, and household dysfunction and the risk of illicit drug use: theadverse childhood experiences study. Pediatrics 111: 564-572.
57. Dunn AJ (2006). Cytokine activation of the HPA axis. Ann NY Acad Sci 917:608-617.
58. Eisenberger NI, Berkman ET, Inagaki TK, Rameson LT, Mashal NM, Irwin MR (2010). Inflammation-induced anhedonia: endotoxin reduces ventral striatum responsesto reward. Biol Psychiatry 68: 748-754.
59. Ekdahl CT, Claasen J-H, Bonde S, Kokaia Z, Lindvall O (2003). Inflammationis detrimental for neurogenesis in adult brain. Proc Natl Acad Sci 100:13632-13637.
60. Eraly SA, Nievergelt CM, Maihofer AX, Barkauskas DA, Biswas N, Agorastos A, et al. (2014). Assessment of plasma C-reactive protein as a biomarker of posttraumaticstress disorder risk. JAMA Psychiatry 71: 423-431.
61. Ernst A, Frisén J (2015). Adult neurogenesis in humans-common and unique traits inmammals. PLoS Biol 13: e1002045.
62. Feng P, Vurbic D, Wu Z, Strohl KP (2007). Brain orexins and wake regulation in ratsexposed to maternal deprivation. Brain Res 1154: 163-172.
63. Fernandes BS, Steiner J, Bernstein H-G, Dodd S, Pasco JA, Dean OM, et al. (2016). C-reactive protein is increased in schizophrenia but is not altered byantipsychotics: meta-analysis and implications. Mol Psychiatry 21: 554-564.
64. Flajnik MF, Du Pasquier L (2004). Evolution of innate and adaptive immunity: can wedraw a line Trends Immunol 25: 640-644.
65. Ford DE, Erlinger TP (2004). Depression and C-reactive protein in US adults: datafrom the Third National Health and Nutrition Examination Survey. Arch Intern Med164: 1010-1014.
66. Frank MG, Watkins LR, Maier SF (2013). Stress-induced glucocorticoids as aneuroendocrine alarm signal of danger. Brain Behav Immun 33: 1-6.
67. Galea I, Bechmann I, Perry VH (2007). What is immune privilege (not) TrendsImmunol 28: 12-18.
68. Ganguly P, Brenhouse HC (2015). Broken or maladaptive Altered trajectories inneuroinflammation and behavior after early life adversity. Dev Cogn Neurosci 11:18-30.
69. Garner CC, Zhai RG, Gundelfinger ED, Ziv NE (2002). Molecular mechanisms ofCNS synaptogenesis. Trends Neurosci 25: 243-250.
70. Giedd JN, Rapoport JL (2010). Structural MRI of pediatric brain development: whathave we learned and where are we going Neuron 67: 728-734.
71. Gleeson M, Bishop NC, Stensel DJ, Lindley MR, Mastana SS, Nimmo MA (2011). The anti-inflammatory effects of exercise: mechanisms and implications for theprevention and treatment of disease. Nat Rev Immunol 11: 607-615.
72. Gogtay N, Giedd JN, Lusk L, Hayashi KM, Greenstein D, Vaituzis AC, et al. (2004). Dynamic mapping of human cortical development during childhood through earlyadulthood. Proc Natl Acad Sci USA 101: 8174-8179.
73. Gouin J-P, Glaser R, Malarkey WB, Beversdorf D, Kiecolt-Glaser JK (2012). Childhood abuse and inflammatory responses to daily stressors. Ann Behav Med44: 287-292.
74. Gould E (2007). How widespread is adult neurogenesis in mammals Nat RevNeurosci 8: 481-488.
75. Greenough WT, Black JE, Wallace CS (1987). Experience and brain development. Child Dev 58: 539-559.
76. Gregor MF, Hotamisligil GS (2011). Inflammatory mechanisms in obesity. Ann RevImmunol 29: 415-445.
77. Gregory AM, Sadeh A (2016). Annual research review: sleep problems in childhoodpsychiatric disorders-a review of the latest science. J Child Psychol Psychiatry57: 296-317.
78. Gunnar M, Quevedo K (2007). The neurobiology of stress and development. AnnRev Psychology 58: 145-173.
79. Hanisch U-K, Kettenmann H (2007). Microglia: active sensor and versatile effectorcells in the normal and pathologic brain. Nat Neurosci 10: 1387-1394.
80. Hannestad J, DellaGioia N, Bloch M (2011). The effect of antidepressant medicationtreatment on serum levels of inflammatory cytokines: a meta-analysis. Neuropsychopharmacology36: 2452-2459.
81. Harrison EL, Baune BT (2014). Modulation of early stress-induced neurobiologicalchanges: a review of behavioural and pharmacological interventions inanimal models. Transl Psychiatry 4: e390.
82. Harrison NA, Brydon L, Walker C, Gray MA, Steptoe A, Critchley HD (2009). Inflammation causes mood changes through alterations in subgenual cingulateactivity and mesolimbic connectivity. Biol Psychiatry 66: 407-414.
83. Hart BL (1988). Biological basis of the behavior of sick animals. Neurosci BiobehavRev 12: 123-137.
84. Hart H, Rubia K (2012). Neuroimaging of child abuse: a critical review. Front HumNeurosci 6: 52.
85. Heim C, Ehlert U, Hellhammer DH (2000). The potential role of hypocortisolism in thepathophysiology of stress-related bodily disorders. Psychoneuroendocrinology25: 1-35.
86. Heim C, Nemeroff CB (2001). The role of childhood trauma in the neurobiology ofmood and anxiety disorders: preclinical and clinical studies. Biol Psychiatry 49:1023-1039.
87. Hennessy MB, Deak T, Schiml-Webb PA (2010a). Early attachment-figure separationand increased risk for later depression: potential mediation by proinflammatoryprocesses. Neurosci Biobehav Rev 34: 782-790.
88. Hennessy MB, Deak T, Schiml-Webb PA, Carlisle CW, O'Brien E (2010b). Maternalseparation produces, and a second separation enhances, core temperatureand passive behavioral responses in guinea pig pups. Physiol Behav 100:305-310.
89. Hensch TK (2005). Critical period plasticity in local cortical circuits. Nat Rev Neurosci6: 877-888.
90. Hodes GE, Pfau ML, Leboeuf M, Golden SA, Christoffel DJ, Bregman D, et al. (2014). Individual differences in the peripheral immune system promote resilience versussusceptibility to social stress. Proc Natl Acad Sci USA 111: 16136-16141.
91. Howren MB, Lamkin DM, Suls J (2009). Associations of depression with C-reactiveprotein, IL-1, and IL-6: a meta-analysis. Psychosom Med 71: 171-186.
92. Hubel DH, Wiesel TN. Brain and visual perception. Oxford University Press: Oxford &New York; (2005).
93. Huh GS, Boulanger LM, Du H, Riquelme PA, Brotz TM, Shatz CJ (2000). Functionalrequirement for class I MHC in CNS development and plasticity. Science 290:2155-2159.
94. Inagaki TK, Muscatell KA, Irwin MR, Cole SW, Eisenberger NI (2012). Inflammationselectively enhances amygdala activity to socially threatening images. Neuroimage59: 3222-3226.
95. Insel TR (2014). The NIMH research domain criteria (RDoC) project: precisionmedicine for psychiatry. Am J Psychiatry 171: 395-397.
96. Irwin MR, Wang M, Campomayor CO, Collado-Hidalgo A, Cole S (2006). Sleepdeprivation and activation of morning levels of cellular and genomic markers ofinflammation. Arch Intern Med 166: 1756-1762.
97. Janeway CA, Medzhitov R (2002). Innate immune recognition. Ann Rev Immunol 20:197-216.
98. Kajeepeta S, Gelaye B, Jackson CL, Williams MA (2015). Adverse childhoodexperiences are associated with adult sleep disorders: a systematic review. SleepMed 16: 320-330.
99. Khandaker GM, Cousins L, Deakin J, Lennox BR, Yolken R, Jones PB (2015). Inflammation and immunity in schizophrenia: implications for pathophysiology andtreatment. Lancet Psychiatry 2: 258-270.
100. Khandaker GM, Pearson RM, Zammit S, Lewis G, Jones PB (2014). Association ofserum interleukin 6 and C-Reactive protein in childhood with depression andpsychosis in young adult life. JAMA Psychiatry 71: 1121-1128.
101. Kiecolt-Glaser JK, Gouin J-P, Weng N-P, Malarkey WB, Beversdorf DQ, Glaser R(2011). Childhood adversity heightens the impact of later-life caregiving stress ontelomere length and inflammation. Psychosom Med 73: 16-22.
102. Kimbrell DA, Beutler B (2001). The evolution and genetics of innate immunity. Nat Rev Genet 2: 256-267.
103. Kipnis J, Gadani S, Derecki NC (2012). Pro-cognitive properties of T cells. Nat RevImmunol 12: 663-669.
104. Kirschbaum C, Pirke KM, Hellhammer DH (1993). The "Trier Social Stress Test-"atool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology 28: 76-81.
105. Klengel T, Mehta D, Anacker C, Rex-Haffner M, Pruessner JC, Pariante CM, et al. (2013). Allele-specific FKBP5 DNA demethylation mediates gene-childhoodtrauma interactions. Nat Neurosci 16: 33-41.
106. Knuesel I, Chicha L, Britschgi M, Schobel SA, Bodmer M, Hellings JA, et al. (2014). Maternal immune activation and abnormal brain development across CNSdisorders. Nat Rev Neurol 10: 643-660.
107. Koh KB, Lee Y, Beyn KM, Chu SH, Kim DM (2008). Counter-stress effects ofrelaxation on proinflammatory and anti-inflammatory cytokines. Brain BehavImmun 22: 1130-1137.
108. Köhler O, Benros ME, Nordentoft M, Farkouh ME, Iyengar RL, Mors O, et al. (2014). Effect of anti-inflammatory treatment on depression, depressive symptoms, andadverse effects: a systematic review and meta-analysis of randomizedclinical trials. JAMA Psychiatry 71: 1381-1391.
109. Leboyer M, Soreca I, Scott J, Frye M, Henry C, Tamouza R, et al. (2012). Can bipolardisorder be viewed as a multi-system inflammatory disease J Affect Disord 141:1-10.
110. Leussis MP, Freund N, Brenhouse HC, Thompson BS, Andersen SL (2012). Depressive-like behavior in adolescents after maternal separation: sex differences,controllability, and GABA. Dev Neurosci 34: 210-217.
111. Levitt P (2003). Structural and functional maturation of the developing primate brain. J Pediatr 143: 35-45.
112. Lewitus GM, Cohen H, Schwartz M (2008). Reducing post-traumatic anxiety byimmunization. Brain Behav Immun 22: 1108-1114.
113. Lewitus GM, Schwartz M (2009). Behavioral immunization: immunity to self-antigenscontributes to psychological stress resilience. Mol Psychiatry 14: 532-536.
114. Lieberam I, Agalliu D, Nagasawa T, Ericson J, Jessell TM (2005). A Cxcl12-CXCR4chemokine signaling pathway defines the initial trajectory of mammalianmotor axons. Neuron 47: 667-679.
115. Luo L, O'Leary DDM (2005). Axon retraction and degeneration in development anddisease. Annu Rev Neurosci 28: 127-156.
116. Lupien SJ, McEwen BS, Gunnar MR, Heim C (2009). Effects of stress throughoutthe lifespan on the brain, behaviour and cognition. Nat Rev Neurosci 10:434-445.
117. MacKinnon DP, Fairchild AJ, Fritz MS (2007). Mediation analysis. Ann Rev Psychol58: 593-614.
118. Macmillan HL, Wathen CN, Barlow J, Fergusson DM, Leventhal JM, Taussig HN(2009). Interventions to prevent child maltreatment and associated impairment. Lancet 373: 250-266.
119. Maes M, Lambrechts J, Bosmans E, Jacobs J, Suy E, Vandervorst C, et al. (1992). Evidence for a systemic immune activation during depression: results of leukocyteenumeration by flow cytometry in conjunction with monoclonal antibody staining. Psychol Med 22: 45-53.
120. Matthews K, Robbins TW (2003). Early experience as a determinant of adultbehavioural responses to reward: the effects of repeated maternal separation inthe rat. Neurosci Biobehav Rev 27: 45-55.
121. Matthews KA, Schott LL, Bromberger JT, Cyranowski JM, Everson-Rose SA,Sowers M (2010). Are there bi-directional associations between depressivesymptoms and C-reactive protein in mid-life women Brain Behav Immun 24:96-101.
122. McCrory EJ, De Brito SA, Kelly PA, Bird G, Sebastian CL, Mechelli A, et al. (2013). Amygdala activation in maltreated children during pre-attentive emotionalprocessing. Br J Psychiatry 202: 269-276.
123. McDade TW (2012). Early environments and the ecology of inflammation. Proc NatlAcad Sci USA 109(Suppl 2): 17281-17288.
124. Medzhitov R, Janeway C (2000). Innate immunity. N Engl J Med 343: 338-344.
125. Mehta MA, Gore-Langton E, Golembo N, Colvert E, Williams SCR, Sonuga-Barke E(2010). Hyporesponsive reward anticipation in the basal ganglia following severeinstitutional deprivation early in life. J Cogn Neurosci 22: 2316-2325.
126. Michopoulos V, Rothbaum AO, Jovanovic T, Almli LM, Bradley B, Rothbaum BOet al (2015). Association of CRP genetic variation and CRP level with elevatedPTSD symptoms and physiological responses in a civilian population with highlevels of trauma. Am J Psychiatry 172: 353-362.
127. Miller AH, Raison CL (2015). The role of inflammation in depression: from evolutionaryimperative to modern treatment target. Nat Rev Immunol 16: 22-34.
128. Miller BJ, Buckley P, Seabolt W, Mellor A, Kirkpatrick B (2011). Meta-analysisof cytokine alterations in schizophrenia: clinical status and antipsychotic effects. Biol Psychiatry 70: 663-671.
129. Miller GE, Cohen S, Ritchey AK (2002). Chronic psychological stress and theregulation of pro-inflammatory cytokines: a glucocorticoid-resistance model. Health Psychol 21: 531-541.
130. Miller GE, Cole SW (2012). Clustering of depression and inflammation in adolescentspreviously exposed to childhood adversity. Biol Psychiatry 72: 34-40.
131. Miller MA, Kandala N-B, Kivimaki M, Kumari M, Brunner EJ, Lowe GDO, et al. (2009). Gender differences in the cross-sectional relationships between sleep durationand markers of inflammation: Whitehall II study. Sleep 32: 857-864.
132. Ming G-L, Song H (2011). Adult neurogenesis in the mammalian brain: significantanswers and significant questions. Neuron 70: 687-702.
133. Mirescu C, Peters JD, Gould E (2004). Early life experience alters response of adultneurogenesis to stress. Nat Neurosci 7: 841-846.
134. Moalem G, Leibowitz-Amit R, Yoles E, Mor F, Cohen IR, Schwartz M (1999). Autoimmune T cells protect neurons from secondary degeneration after centralnervous system axotomy. Nat Med 5: 49-55.
135. Modabbernia A, Taslimi S, Brietzke E, Ashrafi M (2013). Cytokine alterations inbipolar disorder: a meta-analysis of 30 studies. Biol Psychiatry 74: 15-25.
136. Molina PE (2005). Neurobiology of the stress response: contribution of thesympathetic nervous system to the neuroimmune axis in traumatic injury. Shock24: 3-10.
137. Mondelli V, Ciufolini S, Belvederi Murri M, Bonaccorso S, Di Forti M, Giordano A, et al. (2015). Cortisol and inflammatory biomarkers predict poor treatment response infirst episode psychosis. Schizophr Bull 41: 1162-1170.
138. Monje ML, Toda H, Palmer TD (2003). Inflammatory blockade restores adulthippocampal neurogenesis. Science 302: 1760-1765.
139. Mrdalj J, Pallesen S, Milde AM, Jellestad FK, Murison R, Ursin R, et al. (2013). Early and later life stress alter brain activity and sleep in rats. PLoS ONE8: e69923.
140. Musselman DL, Lawson DH, Gumnick JF, Manatunga AK, Penna S, Goodkin RSet al (2001). Paroxetine for the prevention of depression induced by high-doseinterferon alfa. N Engl J Med 344: 961-966.
141. Nanni V, Uher R, Danese A (2012). Childhood maltreatment predicts unfavorablecourse of illness and treatment outcome in depression: a meta-analysis. Am JPsychiatry 169: 141-151.
142. National Research Council (US). (2011). Committee on A Framework for Developing aNew Taxonomy of Disease. National Academies Press (US): Washington (DC).
143. Network and Pathway Analysis Subgroup of Psychiatric Genomics Consortium. (2015). Psychiatric genome-wide association study analyses implicate neuronal,immune and histone pathways. Nat Neurosci 18: 199-209.
144. O'Mahony SM, Marchesi JR, Scully P, Codling C, Ceolho A-M, EMM Quigley, et al. (2009). Early life stress alters behavior, immunity, and microbiota in rats:implications for irritable bowel syndrome and psychiatric illnesses. Biol Psychiatry65: 263-267.
145. Pace TWW, Mletzko TC, Alagbe O, Musselman DL, Nemeroff CB, Miller AH, et al. (2006). Increased stress-induced inflammatory responses in male patients withmajor depression and increased early life stress. Am J Psychiatry 163:1630-1633.
146. Pace TWW, Negi LT, Dodson-Lavelle B, Ozawa-de Silva B, Reddy SD, Cole SP, et al. (2013). Engagement with Cognitively-Based Compassion Training is associatedwith reduced salivary C-reactive protein from before to after training in foster careprogram adolescents. Psychoneuroendocrinology 38: 294-299.
147. Paolicelli RC, Bolasco G, Pagani F, Maggi L, Scianni M, Panzanelli P, et al. (2011). Synaptic pruning by microglia is necessary for normal brain development. Science333: 1456-1458.
148. Pariante CM, Miller AH (2001). Glucocorticoid receptors in major depression:relevance to pathophysiology and treatment. Biol Psychiatry 49: 391-404.
149. Passos IC, Vasconcelos-Moreno MP, Costa LG, Kunz M, Brietzke E, Quevedo Jet al (2015). Inflammatory markers in post-traumatic stress disorder: a systematicreview, meta-analysis, and meta-regression. Lancet Psychiatry 2: 1002-1012.
150. Patterson PH (2009). Immune involvement in schizophrenia and autism: etiology,pathology and animal models. Behav Brain Res 204: 313-321.
151. Pechtel P, Pizzagalli DA (2011). Effects of early life stress on cognitive and affectivefunction: an integrated review of human literature. Psychopharmacology 214:55-70.
152. Peferoen L, Kipp M, van der Valk P, van Noort JM, Amor S (2014). Oligodendrocytemicrogliacross-talk in the central nervous system. Immunology 141: 302-313.
153. Perry VH, Holmes C (2014). Microglial priming in neurodegenerative disease. NatRev Neurol 10: 217-224.
154. Perry VH, Newman TA, Cunningham C (2003). The impact of systemic infection onthe progression of neurodegenerative disease. Nat Rev Neurosci 4: 103-112.
155. Petanjek Z, Judaš M, Šimic G, Rasin MR, Uylings HBM, Rakic P, et al. (2011). Extraordinary neoteny of synaptic spines in the human prefrontal cortex. Proc NatlAcad Sci USA 108: 13281-13286.
156. Pollak SD, Kistler DJ (2002). Early experience is associated with the development ofcategorical representations for facial expressions of emotion. Proc Natl Acad Sci99: 9072-9076.
157. Poulton R, Moffitt TE, Silva PA (2015). The Dunedin Multidisciplinary Healthand Development Study: overview of the first 40 years, with an eye to the future. Soc Psychiatry Psychiatr Epidemiol 50: 679-693.
158. Raison CL, Miller AH (2003). When not enough is too much: the role of insufficientglucocorticoid signaling in the pathophysiology of stress-related disorders. Am JPsychiatry 160: 1554-1565.
159. Raison CL, Rutherford RE, Woolwine BJ, Shuo C, Schettler P, Drake DF, et al. (2013). A randomized controlled trial of the tumor necrosis factor antagonist infliximab fortreatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry 70: 31-41.
160. Raznahan A, Shaw PW, Lerch JP, Clasen LS, Greenstein D, Berman R, et al. (2014). Longitudinal four-dimensional mapping of subcortical anatomy in humandevelopment. Proc Natl Acad Sci USA 111: 1592-1597.
161. Redlich R, Stacey D, Opel N, Grotegerd D, Dohm K, Kugel H, et al. (2015). Evidenceof an IFN-by early life stress interaction in the regulation of amygdala reactivity toemotional stimuli. Psychoneuroendocrinology 62: 166-173.
162. Reichenberg A, Yirmiya R, Schuld A, Kraus T, Haack M, Morag A, et al. (2001). Cytokine-associated emotional and cognitive disturbances in humans. Arch GenPsychiatry 58: 445-452.
163. Rook GA, Stanford JL (1998). Give us this day our daily germs. Immunol Today 19:113-116.
164. Rook GAW, Lowry CA, Raison CL (2015). Hygiene and other early childhood influenceson the subsequent function of the immune system. Brain Res 1617: 47-62.
165. Schedlowski M, Engler H, Grigoleit J-S (2014). Endotoxin-induced experimentalsystemic inflammation in humans: a model to disentangle immune-to-braincommunication. Brain Behav Immun 35: 1-8.
166. Setiawan E, Wilson AA, Mizrahi R, Rusjan PM, Miler L, Rajkowska G, et al. (2015). Role of translocator protein density, a marker of neuroinflammation, in the brainduring major depressive episodes. JAMA Psychiatry 72: 268-275.
167. Shanks N, Larocque S, Meaney MJ (1995). Neonatal endotoxin exposure alters thedevelopment of the hypothalamic-pituitary-adrenal axis: early illness and laterresponsivity to stress. J Neurosci 15: 376-384.
168. Shanks N, Lightman SL (2001). The maternal-neonatal neuro-immune interface: arethere long-term implications for inflammatory or stress-related disease J ClinInvest 108: 1567-1573.
169. Shanks N, Windle RJ, Perks PA, Harbuz MS, Jessop DS, Ingram CD, et al. (2000). Early-life exposure to endotoxin alters hypothalamic-pituitary-adrenal function andpredisposition to inflammation. Proc Natl Acad Sci 97: 5645-5650.
170. Shatz CJ (2009). MHC class I: an unexpected role in neuronal plasticity. Neuron 64:40-45.
171. Shaw P, Eckstrand K, Sharp W, Blumenthal J, Lerch JP, Greenstein D, et al. (2007). Attention-deficit/hyperactivity disorder is characterized by a delay in corticalmaturation. Proc Natl Acad Sci USA 104: 19649-19654.
172. Shaw P, Greenstein D, Lerch J, Clasen L, Lenroot R, Gogtay N, et al. (2006). Intellectual ability and cortical development in children and adolescents. Nature440: 676-679.
173. Sherman DL, Brophy PJ (2005). Mechanisms of axon ensheathment andmyelin growth. Nat Rev Neurosci 6: 683-690.
174. Shiels MS, Katki HA, Freedman ND, Purdue MP, Wentzensen N, Trabert B, et al. (2014). Cigarette smoking and variations in systemic immune and inflammationmarkers. J Natl Cancer Inst 106: dju294-dju294.
175. Shirtcliff EA, Coe CL, Pollak SD (2009). Early childhood stress is associated withelevated antibody levels to herpes simplex virus type 1. Proc Natl Acad Sci USA106: 2963-2967.
176. Short SJ, Lubach GR, Karasin AI, Olsen CW, Styner M, Knickmeyer RC, et al. (2010). Maternal influenza infection during pregnancy impacts postnatal brain developmentin the rhesus monkey. Biol Psychiatry 67: 965-973.
177. Slopen N, Kubzansky LD, McLaughlin KA, Koenen KC (2013). Childhood adversityand inflammatory processes in youth: a prospective study. Psychoneuroendocrinology38: 188-200.
178. Smith RS (1991). The macrophage theory of depression. Med Hypotheses 35:298-306.
179. Solomon GF, Levine S, Kraft JK (1968). Early experience and immunity. Nature 220:821-822.
180. Stellwagen D, Malenka RC (2006). Synaptic scaling mediated by glial TNF-alpha. Nature 440: 1054-1059.
181. Stephan AH, Barres BA, Stevens B (2012). The complement system: an unexpectedrole in synaptic pruning during development and disease. Annu Rev Neurosci 35:369-389.
182. Steptoe A, Hamer M, Chida Y (2007a). The effects of acute psychological stress oncirculating inflammatory factors in humans: a review and meta-analysis. BrainBehav Immun 21: 901-912.
183. Steptoe A, Hamer M, Chida Y (2007b). The effects of acute psychological stress oncirculating inflammatory factors in humans: a review and meta-analysis. BrainBehav Immun 21: 901-912.
184. Strachan DP (2000). Family size, infection and atopy: the first decade of the "hygienehypothesis". Thorax 55(Suppl 1): S2-S10.
185. Strawbridge R, Arnone D, Danese A, Papadopoulos A, Herane Vives A, Cleare AJ(2015). Inflammation and clinical response to treatment in depression: a metaanalysis. Eur Neuropsychopharmacol 25: 1532-1543.
186. Takatsuru Y, Nabekura J, Ishikawa T, Kohsaka S-I, Koibuchi N (2015). Early-lifestress increases the motility of microglia in adulthood. J Physiol Sci 65: 187-194.
187. Takizawa R, Danese A, Maughan B, Arseneault L (2015). Bullying victimization inchildhood predicts inflammation and obesity at mid-life: a five-decade birthcohort study. Psychol Med 45: 2705-2715.
188. Tau GZ, Peterson BS (2010). Normal development of brain circuits. Neuropsychopharmacology35: 147-168.
189. Terr LC (1991). Childhood traumas: an outline and overview. Am J Psychiatry 148:10-20.
190. Thornton LM, Andersen BL, Schuler TA, Carson WE (2009). A psychologicalintervention reduces inflammatory markers by alleviating depressive symptoms:secondary analysis of a randomized controlled trial. Psychosom Med 71:715-724.
191. Tiba PA, Tufik S, Suchecki D (2004). Effects of maternal separation on baselinesleep and cold stress-induced sleep rebound in adult Wistar rats. Sleep 27:1146-1153.
192. Tottenham N, Hare TA, Millner A, Gilhooly T, Zevin JD, Casey BJ (2011). Elevated amygdala response to faces following early deprivation. Dev Sci 14:190-204.
193. Tottenham N, Sheridan MA (2009). A review of adversity, the amygdala and thehippocampus: a consideration of developmental timing. Front Hum Neurosci3: 68.
194. Tran PB, Miller RJ (2003). Chemokine receptors: signposts to brain developmentand disease. Nat Rev Neurosci 4: 444-455.
195. Turrigiano GG (2008). The self-tuning neuron: synaptic scaling of excitatorysynapses. Cell 135: 422-435.
196. Uematsu A, Matsui M, Tanaka C, Takahashi T, Noguchi K, Suzuki M, et al. (2012). Developmental trajectories of amygdala and hippocampus from infancy to earlyadulthood in healthy individuals. PLoS ONE 7: e46970.
197. van der Worp HB, Howells DW, Sena ES, Porritt MJ, Rewell S, O'Collins V, et al. (2010). Can animal models of disease reliably inform human studies PLoS Med7: e1000245.
198. van Harmelen A-L, van Tol M-J, Demenescu LR, van der Wee NJA, Veltman DJ,Aleman A, et al. (2013). Enhanced amygdala reactivity to emotional faces in adultsreporting childhood emotional maltreatment. Soc Cogn Affect Neurosci 8:362-369.
199. Varese F, Smeets F, Drukker M, Lieverse R, Lataster T, Viechtbauer W, et al. (2012). Childhood adversities increase the risk of psychosis: a meta-analysis of patientcontrol,prospective-and cross-sectional cohort studies. Schizophr Bull 38:661-671.
200. Viviani B, Boraso M, Valero M, Gardoni F, Marco EM, Llorente R, et al. (2014). Earlymaternal deprivation immunologically primes hippocampal synapses byredistributing interleukin-1 receptor type I in a sex dependent manner. BrainBehav Immun 35: 135-143.
201. Weaver ICG, Cervoni N, Champagne FA, D'Alessio AC, Sharma S, Seckl JRet al (2004). Epigenetic programming by maternal behavior. Nat Neurosci 7:847-854.
202. Wei L, Simen A, Mane S, Kaffman A (2012). Early life stress inhibits expression of anovel innate immune pathway in the developing hippocampus. Neuropsychopharmacology37: 567-580.
203. Widom CS (1999). Posttraumatic stress disorder in abused and neglected childrengrown up. Am J Psychiatry 156: 1223-1229.
204. Widom CS, DuMont K, Czaja SJ (2007). A prospective investigation of majordepressive disorder and comorbidity in abused and neglected children grown up. Arch Gen Psychiatry 64: 49-56.
205. Wieck A, Andersen SL, Brenhouse HC (2013). Evidence for a neuroinflammatorymechanism in delayed effects of early life adversity in rats: relationship to corticalNMDA receptor expression. Brain Behav Immun 28: 218-226.
206. Ygberg S, Nilsson A (2012). The developing immune system-from foetus to toddler. Acta Paediatr 101: 120-127.
207. Yirmiya R, Goshen I (2011). Immune modulation of learning, memory, neuralplasticity and neurogenesis. Brain Behav Immun 25: 181-213.
208. Yoles E, Hauben E, Palgi O, Agranov E, Gothilf A, Cohen A, et al. (2001). Protectiveautoimmunity is a physiological response to CNS trauma. J Neurosci 21:3740-3748.
209. Ziv Y, Ron N, Butovsky O, Landa G, Sudai E, Greenberg N, et al. (2006). Immune cellscontribute to the maintenance of neurogenesis and spatial learning abilities inadulthood. Nat Neurosci 9: 268-275.