Neuropsychology Review

, Volume 28, Issue 2, pp 123–175 | Cite as

Neurodevelopmental consequences of pediatric cancer and its treatment: applying an early adversity framework to understanding cognitive, behavioral, and emotional outcomes

  • Hilary A. MarusakEmail author
  • Allesandra S. Iadipaolo
  • Felicity W. Harper
  • Farrah Elrahal
  • Jeffrey W. Taub
  • Elimelech Goldberg
  • Christine A. Rabinak


Today, children are surviving pediatric cancer at unprecedented rates, making it one of modern medicine’s true success stories. However, we are increasingly becoming aware of several deleterious effects of cancer and the subsequent “cure” that extend beyond physical sequelae. Indeed, survivors of childhood cancer commonly report cognitive, emotional, and psychological difficulties, including attentional difficulties, anxiety, and posttraumatic stress symptoms (PTSS). Cognitive late- and long-term effects have been largely attributed to neurotoxic effects of cancer treatments (e.g., chemotherapy, cranial irradiation, surgery) on brain development. The role of childhood adversity in pediatric cancer – namely, the presence of a life-threatening disease and endurance of invasive medical procedures – has been largely ignored in the existing neuroscientific literature, despite compelling research by our group and others showing that exposure to more commonly studied adverse childhood experiences (i.e., domestic and community violence, physical, sexual, and emotional abuse) strongly imprints on neural development. While these adverse childhood experiences are different in many ways from the experience of childhood cancer (e.g., context, nature, source), they do share a common element of exposure to threat (i.e., threat to life or physical integrity). Therefore, we argue that the double hit of early threat and cancer treatments likely alters neural development, and ultimately, cognitive, behavioral, and emotional outcomes. In this paper, we (1) review the existing neuroimaging research on child, adolescent, and adult survivors of childhood cancer, (2) summarize gaps in our current understanding, (3) propose a novel neurobiological framework that characterizes childhood cancer as a type of childhood adversity, particularly a form of early threat, focusing on development of the hippocampus and the salience and emotion network (SEN), and (4) outline future directions for research.


Childhood cancer pediatric oncology leukemia brain tumor brain 



We would like to thank the young cancer survivors and their families for participating in our research and more importantly, for sharing their stories about their experiences with us.


None. Dr. MaCociety award 129368-PF-16-057-01-PCSM. Dr. Rabinak is supported by National Institute of Mental Health grants K01MH101123 and R61MH111935.


  1. Aber, J. L., Bennett, N. G., Conley, D. C., & Li, J. (1997). The effects of poverty on child health and development. Annual review of public health, 18(1), 463–483.PubMedCrossRefGoogle Scholar
  2. Ainsworth, M. S. (1979). Infant–mother attachment. American psychologist, 34(10), 932.PubMedCrossRefGoogle Scholar
  3. Alderfer, M. A., & Kazak, A. E. (2006). Family issues when a child is on treatment for cancer. In Comprehensive handbook of childhood cancer and sickle cell disease: A biopsychosocial approach (pp. 53–74). New York: Oxford University Press.Google Scholar
  4. Alderfer, M. A., Labay, L. E., & Kazak, A. E. (2003). Brief report: does posttraumatic stress apply to siblings of childhood cancer survivors? Journal of pediatric psychology, 28(4), 281–286.PubMedCrossRefGoogle Scholar
  5. Anderson, F. S., & Kunin-Batson, A. S. (2009). Neurocognitive late effects of chemotherapy in children: The past 10 years of research on brain structure and function. Pediatric Blood & Cancer, 52(2), 159–164. Scholar
  6. Armstrong, G. T., Reddick, W. E., Petersen, R. C., Santucci, A., Zhang, N., Srivastava, D., et al. (2013). Evaluation of memory impairment in aging adult survivors of childhood acute lymphoblastic leukemia treated with cranial radiotherapy. Journal of the National Cancer Institute, 105(12), 899–907.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Ashford, J., Schoffstall, C., Reddick, W. E., Leone, C., Laningham, F. H., Glass, J. O., et al. (2010). Attention and Working Memory Abilities in Children Treated for Acute Lymphoblastic Leukemia. Cancer, 116(19), 4638–4645. Scholar
  8. American Psychiatric Association. (2013). Trauma- and stressor-related disorders. In Diagnostic and statistical manual of mental disorders (5th ed.). Washington D.C.: American Psychiatric Publishing.Google Scholar
  9. Aukema, E. J., Caan, M. W., Oudhuis, N., Majoie, C. B., Vos, F. M., Reneman, L., et al. (2009). White matter fractional anisotropy correlates with speed of processing and motor speed in young childhood cancer survivors. International Journal of Radiation Oncology* Biology* Physics, 74(3), 837–843.CrossRefGoogle Scholar
  10. Badr, M. A., Hassan, T. H., El-Gerby, K. M., & Lamey, M. E. (2013). Magnetic resonance imaging of the brain in survivors of childhood acute lymphoblastic leukemia. Oncology Letters, 5, 621–626.Google Scholar
  11. Baron Nelson, M., Compton, P., Macey, P. M., Patel, S. K., Jacob, E., O’Neil, S., … Harper, R. M. (2016). Diffusion Tensor Imaging and Neurobehavioral Outcome in Children With Brain Tumors Treated With Chemotherapy. Journal of Pediatric Oncology Nursing, 33(2), 119–128.Google Scholar
  12. Bemis, H., Yarboi, J., Gerhardt, C. A., Vannatta, K., Desjardins, L., Murphy, L. K., et al. (2015). Childhood cancer in context: sociodemographic factors, stress, and psychological distress among mothers and children. Journal of pediatric psychology, 40(8), 733–743.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Berridge, K. C. (2007). The debate over dopamine’s role in reward: the case for incentive salience. Psychopharmacology, 191(3), 391–431.PubMedCrossRefGoogle Scholar
  14. Bessell, A. G. (2001). Children surviving cancer: Psychosocial adjustment, quality of life, and school experiences. Exceptional Children, 67(3), 345–359.CrossRefGoogle Scholar
  15. Bhojwani, D., Sabin, N. D., Pei, D., Yang, J. J., Khan, R. B., Panetta, J. C., et al. (2014). Methotrexate-induced neurotoxicity and leukoencephalopathy in childhood acute lymphoblastic leukemia. Journal of clinical oncology, 32(9), 949–959.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Bitsko, M. J., Cohen, D., Dillon, R., Harvey, J., Krull, K., & Klosky, J. L. (2016). Psychosocial Late Effects in Pediatric Cancer Survivors: A Report From the Children's Oncology Group. Pediatric Blood & Cancer, 63(2), 337–343. Scholar
  17. Bogdan, R., Nikolova, Y. S., & Pizzagalli, D. A. (2013). Neurogenetics of depression: a focus on reward processing and stress sensitivity. Neurobiology of disease, 52, 12–23.PubMedCrossRefGoogle Scholar
  18. Brinkman, T. M., Reddick, W. E., Luxton, J., Glass, J. O., Sabin, N. D., Srivastava, D. K., et al. (2012). Cerebral white matter integrity and executive function in adult survivors of childhood medulloblastoma. Neuro-Oncology, 14(suppl 4), iv25–iv36.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Bruce, M. (2006). A systematic and conceptual review of posttraumatic stress in childhood cancer survivors and their parents. Clinical psychology review, 26(3), 233–256.PubMedCrossRefGoogle Scholar
  20. Buizer, A. I., De Sonneville, L. M., Van Den Heuvel-eibrink, M. M., Njiokiktjien, C., & Veerman, A. J. (2005a). Visuomotor control in survivors of childhood acute lymphoblastic leukemia treated with chemotherapy only. Journal of the International Neuropsychological Society, 11(05), 554–565.PubMedCrossRefGoogle Scholar
  21. Buizer, A. I., de Sonneville, L. M., van den HeuvelEibrink, M. M., & Veerman, A. J. (2005b). Chemotherapy and attentional dysfunction in survivors of childhood acute lymphoblastic leukemia: effect of treatment intensity. Pediatric blood & cancer, 45(3), 281–290.CrossRefGoogle Scholar
  22. Butler, R. W., & Haser, J. K. (2006). Neurocognitive effects of treatment for childhood cancer. Mental Retardation and Developmental Disabilities Research Reviews, 12(3), 184–191. Scholar
  23. Buzsáki, G., & Moser, E. I. (2013). Memory, navigation and theta rhythm in the hippocampal-entorhinal system. Nature neuroscience, 16(2), 130–138.PubMedPubMedCentralCrossRefGoogle Scholar
  24. Carey, M., Haut, M., Reminger, S., Hutter, J., Theilmann, R., & Kaemingk, K. (2008). Reduced frontal white matter volume in long-term childhood leukemia survivors: a voxel-based morphometry study. American Journal of Neuroradiology, 29(4), 792–797.Google Scholar
  25. Carrion, V. G., Garrett, A., Menon, V., Weems, C. F., & Reiss, A. L. (2008). Posttraumatic stress symptoms and brain function during a response-inhibition task: an fMRI study in youth. Depression and anxiety, 25(6), 514–526.PubMedCrossRefGoogle Scholar
  26. Caspi, A., Houts, R. M., Belsky, D. W., Goldman-Mellor, S. J., Harrington, H., Israel, S., et al. (2014). The p Factor: One General Psychopathology Factor in the Structure of Psychiatric Disorders? Clinical psychological science : a journal of the Association for Psychological Science, 2(2), 119–137. Scholar
  27. Castellino, S. M., Ullrich, N. J., Whelen, M. J., & Lange, B. J. (2014). Developing interventions for cancer-related cognitive dysfunction in childhood cancer survivors. Journal of the National Cancer Institute, 106(8), dju186.Google Scholar
  28. Chen, E., & Miller, G. E. (2013). Socioeconomic status and health: mediating and moderating factors. Annual Review of Clinical Psychology, 9, 723–749.PubMedCrossRefGoogle Scholar
  29. Chen, H., Wang, L., King, T. Z., & Mao, H. (2016). Increased frontal functional networks in adult survivors of childhood brain tumors. NeuroImage: Clinical, 11, 339–346.CrossRefGoogle Scholar
  30. Cheung, Y. T., & Krull, K. R. (2015). Neurocognitive outcomes in long-term survivors of childhood acute lymphoblastic leukemia treated on contemporary treatment protocols: A systematic review. Neuroscience & Biobehavioral Reviews, 53, 108–120.CrossRefGoogle Scholar
  31. Cheung, Y. T., Sabin, N. D., Reddick, W. E., Bhojwani, D., Liu, W., Brinkman, T. M., et al. (2016). Leukoencephalopathy and long-term neurobehavioural, neurocognitive, and brain imaging outcomes in survivors of childhood acute lymphoblastic leukaemia treated with chemotherapy: a longitudinal analysis. The Lancet Haematology, 3(10), e456–e466.PubMedPubMedCentralCrossRefGoogle Scholar
  32. Chu, W. C., Chik, K.-w., Chan, Y.-l., Yeung, D. K., Roebuck, D. J., Howard, R. G., … Metreweli, C. (2003). White matter and cerebral metabolite changes in children undergoing treatment for acute lymphoblastic leukemia: longitudinal study with MR imaging and 1H MR spectroscopy. Radiology, 229(3), 659–669.Google Scholar
  33. Cline, R. J., Harper, F. W., Penner, L. A., Peterson, A. M., Taub, J. W., & Albrecht, T. L. (2006). Parent communication and child pain and distress during painful pediatric cancer treatments. Social science & medicine, 63(4), 883–898.CrossRefGoogle Scholar
  34. Cole, P. D., Finkelstein, Y., Stevenson, K. E., Blonquist, T. M., Vijayanathan, V., Silverman, L. B., et al. (2015). Polymorphisms in Genes Related to Oxidative Stress Are Associated With Inferior Cognitive Function After Therapy for Childhood Acute Lymphoblastic Leukemia. J Clin Oncol, 33(19), 2205–2211. Scholar
  35. Conklin, H., Krull, K., Reddick, W., Pei, D., Cheng, C., & Pui, C. (2012a). Cognitive outcomes following contemporary treatment without cranial irradiation for childhood acute lymphoblastic leukemia. Journal of the National Cancer Institute, 104(18), 1386–1395.PubMedPubMedCentralCrossRefGoogle Scholar
  36. Conklin, H. M., Krull, K. R., Reddick, W. E., Pei, D., Cheng, C., & Pui, C. H. (2012b). Cognitive outcomes following contemporary treatment without cranial irradiation for childhood acute lymphoblastic leukemia. J Natl Cancer Inst, 104(18), 1386–1395. Scholar
  37. Conklin, H. M., Ogg, R. J., Ashford, J. M., Scoggins, M. A., Zou, P., Clark, K. N., et al. (2015). Computerized cognitive training for amelioration of cognitive late effects among childhood cancer survivors: a randomized controlled trial. Journal of clinical oncology, 33(33), 3894–3902.PubMedPubMedCentralCrossRefGoogle Scholar
  38. Conklin, H. M., Ashford, J. M., Clark, K. N., Martin-Elbahesh, K., Hardy, K. K., Merchant, T. E., et al. (2016). Long-term efficacy of computerized cognitive training among survivors of childhood cancer: A single-blind randomized controlled trial. Journal of Pediatric Psychology, 42, 220–231.Google Scholar
  39. Correa, D. D., & Ahles, T. A. (2008). Neurocognitive changes in cancer survivors. Cancer J, 14(6), 396–400. Scholar
  40. De Clercq, B., De Fruyt, F., Koot, H. M., & Benoit, Y. (2004). Quality of life in children surviving cancer: a personality and multi-informant perspective. Journal of pediatric psychology, 29(8), 579–590.PubMedCrossRefGoogle Scholar
  41. Dellani, P. R., Eder, S., Gawehn, J., Vucurevic, G., Fellgiebel, A., Müller, M. J., et al. (2008). Late structural alterations of cerebral white matter in long-term survivors of childhood leukemia. Journal of Magnetic Resonance Imaging, 27(6), 1250–1255.PubMedCrossRefGoogle Scholar
  42. De Smet, H. J., Baillieux, H., Wackenier, P., De Praeter, M., Engelborghs, S., Paquier, P. F., … Mariën, P. (2009). Long-term cognitive deficits following posterior fossa tumor resection: a neuropsychological and functional neuroimaging follow-up study. Neuropsychology, 23(6), 694.Google Scholar
  43. Dietrich, J., Prust, M., & Kaiser, J. (2015). Chemotherapy, cognitive impairment and hippocampal toxicity. Neuroscience, 309, 224–232.PubMedCrossRefGoogle Scholar
  44. Duffner, P. K., Armstrong, F. D., Chen, L., Helton, K., Brecher, M. L., Bell, B., & Chauvenet, A. R. (2014). Neurocognitive and neuroradiologic central nervous system late effects in children treated on Pediatric Oncology Group (POG) P9605 (standard risk) and P9201 (lesser risk) acute lymphoblastic leukemia protocols (ACCL0131): a methotrexate consequence? A report from the Children's Oncology Group. Journal of Pediatric Hematology/Oncology, 36(1), 8.Google Scholar
  45. Duran, B. (2013a). Posttraumatic growth as experienced by childhood cancer survivors and their families: a narrative synthesis of qualitative and quantitative research. Journal of pediatric oncology nursing, 30(4), 179–197.PubMedCrossRefGoogle Scholar
  46. Duran, B. (2013b). Posttraumatic growth as experienced by childhood cancer survivors and their families: a narrative synthesis of qualitative and quantitative research. J Pediatr Oncol Nurs, 30(4), 179–197. Scholar
  47. Edelmann, M. N., Ogg, R. J., Scoggins, M. A., Brinkman, T. M., Sabin, N. D., Pui, C. H., … Krull, K. R. (2013). Dexamethasone exposure and memory function in adult survivors of childhood acute lymphoblastic leukemia: A report from the SJLIFE cohort. Pediatric Blood & Cancer, 60(11), 1778–1784.Google Scholar
  48. Edelmann, M. N., Krull, K. R., Liu, W., Glass, J. O., Ji, Q., Ogg, R. J., et al. (2014). Diffusion tensor imaging and neurocognition in survivors of childhood acute lymphoblastic leukaemia. Brain, 137(11), 2973–2983.PubMedPubMedCentralCrossRefGoogle Scholar
  49. Ehrhardt, M.J., Sandlund, J.T., Zhang, N., Liu, W., Ness, K.K., Bhakta, N., Chemaitilly, W., et al. (2017) Late outcomes of adult survivors of childhood non-Hodgkin lymphoma: A report from the St. Jude lifetime cohort study. Pediatric Blood & Cancer, 64.
  50. Eisenberg, N., Fabes, R. A., Guthrie, I. K., & Reiser, M. (2000). Dispositional emotionality and regulation: their role in predicting quality of social functioning. Journal of personality and social psychology, 78(1), 136.PubMedCrossRefGoogle Scholar
  51. Eiser, C., Hill, J. J., & Vance, Y. H. (2000). Examining the psychological consequences of surviving childhood cancer: systematic review as a research method in pediatric psychology. Journal of pediatric psychology, 25(6), 449–460.PubMedCrossRefGoogle Scholar
  52. ElAlfy, M., Ragab, I., Azab, I., Amin, S., & Abdel-Maguid, M. (2014). Neurocognitive outcome and white matter anisotropy in childhood acute lymphoblastic leukemia survivors treated with different protocols. Pediatric hematology and oncology, 31(2), 194–204.PubMedCrossRefGoogle Scholar
  53. Erickson, S. J., & Steiner, H. (2001). Trauma and personality correlates in long term pediatric cancer survivors. Child Psychiatry & Human Development, 31(3), 195–213.CrossRefGoogle Scholar
  54. Etkin, A., & Wager, T. D. (2007). Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. American Journal of Psychiatry, 164(10), 1476–1488.PubMedPubMedCentralCrossRefGoogle Scholar
  55. Etkin, A., Egner, T., & Kalisch, R. (2011). Emotional processing in anterior cingulate and medial prefrontal cortex. Trends in cognitive sciences, 15(2), 85–93.PubMedCrossRefGoogle Scholar
  56. Etkin, A., Büchel, C., & Gross, J. J. (2015). The neural bases of emotion regulation. Nature reviews neuroscience, 16(11), 693–700.PubMedCrossRefGoogle Scholar
  57. Felitti, V. J., Anda, R. F., Nordenberg, D., Williamson, D. F., Spitz, A. M., Edwards, V., et al. (1998). Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults: The Adverse Childhood Experiences (ACE) Study. American journal of preventive medicine, 14(4), 245–258.PubMedCrossRefGoogle Scholar
  58. Ficek, K., Blamek, S., Syguła, D., Miszczyk, L., Sońta-Jakimczyk, D., & Tarnawski, R. (2010). Evaluation of the late effects of CNS prophylactic treatment in childhood acute lymphoblastic leukemia (ALL) using magnetic resonance spectroscopy Brain Edema XIV (pp. 195–197): Springer.Google Scholar
  59. Finkelhor, D. (2009). Children’s exposure to violence: A comprehensive national survey. Washington, DC: U.S. Department of Justice, Office of Justice Programs, Office of Juvenile Justice and Delinquency Prevention.Google Scholar
  60. Fox, M. D., & Raichle, M. E. (2007). Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nature reviews neuroscience, 8(9), 700–711.PubMedCrossRefGoogle Scholar
  61. Fujisawa, T. X., Jung, M., Kojima, M., Saito, D. N., Kosaka, H., & Tomoda, A. (2015). Neural basis of psychological growth following adverse experiences: a resting-state functional MRI study. PloS one, 10(8), e0136427.PubMedPubMedCentralCrossRefGoogle Scholar
  62. Genschaft, M., Huebner, T., Plessow, F., Ikonomidou, V. N., Abolmaali, N., Krone, F., et al. (2013). Impact of chemotherapy for childhood leukemia on brain morphology and function. PloS one, 8(11), e78599.PubMedPubMedCentralCrossRefGoogle Scholar
  63. Ghetti, S., & Bunge, S. A. (2012). Neural changes underlying the development of episodic memory during middle childhood. Developmental cognitive neuroscience, 2(4), 381–395.PubMedPubMedCentralCrossRefGoogle Scholar
  64. Gianinazzi, M. E., Rueegg, C. S., Vetsch, J., Luer, S., Kuehni, C. E., & Michel, G. (2016). Cancer's positive flip side: posttraumatic growth after childhood cancer. Support Care Cancer, 24(1), 195–203. Scholar
  65. Gillespie, C. F., Bradley, B., Mercer, K., Smith, A. K., Conneely, K., Gapen, M., et al. (2009). Trauma exposure and stress-related disorders in inner city primary care patients. General hospital psychiatry, 31(6), 505–514.PubMedPubMedCentralCrossRefGoogle Scholar
  66. Gogtay, N., & Thompson, P. M. (2010). Mapping gray matter development: implications for typical development and vulnerability to psychopathology. Brain and cognition, 72(1), 6–15.PubMedCrossRefGoogle Scholar
  67. Guyer, A. E., Kaufman, J., Hodgdon, H. B., Masten, C. L., Jazbec, S., Pine, D. S., et al. (2006). Behavioral alterations in reward system function: the role of childhood maltreatment and psychopathology. Journal of the American Academy of Child & Adolescent Psychiatry, 45(9), 1059–1067.CrossRefGoogle Scholar
  68. Hackman, D. A., & Farah, M. J. (2009). Socioeconomic status and the developing brain. Trends in cognitive sciences, 13(2), 65–73.PubMedPubMedCentralCrossRefGoogle Scholar
  69. Hamilton, J. P., Etkin, A., Furman, D. J., Lemus, M. G., Johnson, R. F., & Gotlib, I. H. (2012). Functional neuroimaging of major depressive disorder: a meta-analysis and new integration of baseline activation and neural response data. American Journal of Psychiatry, 169(7), 693–703.PubMedCrossRefGoogle Scholar
  70. Hanson, J. L., Knodt, A. R., Brigidi, B. D., & Hariri, A. R. (2015). Lower structural integrity of the uncinate fasciculus is associated with a history of child maltreatment and future psychological vulnerability to stress. Development and Psychopathology, 27(4pt2), 1611–1619.PubMedPubMedCentralCrossRefGoogle Scholar
  71. Harila-Saari, A. H., Pääkkö, E. L., Vainionpää, L. K., Pyhtinen, J., & Lanning, B. M. (1998). A longitudinal magnetic resonance imaging study of the brain in survivors of childhood acute lymphoblastic leukemia. Cancer, 83(12), 2608–2617.Google Scholar
  72. Harper, K., Felicity, W., Schmidt, J. E., Beacham, A. O., Salsman, J. M., Averill, A. J., et al. (2007). The role of social cognitive processing theory and optimism in positive psychosocial and physical behavior change after cancer diagnosis and treatment. Psycho-Oncology, 16(1), 79–91.CrossRefGoogle Scholar
  73. Harper, F. W., Peterson, A. M., Uphold, H., Albrecht, T. L., Taub, J. W., Orom, H., et al. (2013). Longitudinal study of parent caregiving self-efficacy and parent stress reactions with pediatric cancer treatment procedures. Psycho-Oncology, 22(7), 1658–1664.PubMedCrossRefGoogle Scholar
  74. Harper, F. W., Goodlett, B. D., Trentacosta, C. J., Albrecht, T. L., Taub, J. W., Phipps, S., et al. (2014a). Temperament, personality, and quality of life in pediatric cancer patients. Journal of pediatric psychology, 39(4), 459–468.PubMedPubMedCentralCrossRefGoogle Scholar
  75. Harper, F. W., Peterson, A. M., Albrecht, T. L., Taub, J. W., Phipps, S., & Penner, L. A. (2014b). Posttraumatic stress symptoms in parents of pediatric cancer patients: A mediational analysis. Journal of Traumatic Stress Disorders & Treatment, 3(4).Google Scholar
  76. Harper, F. W., Peterson, A. M., Albrecht, T. L., Taub, J. W., Phipps, S., & Penner, L. A. (2015). Satisfaction with support versus size of network: Differential effects of social support on psychological distress in parents of pediatric cancer patients. Psycho-Oncology, 25, 551–558.Google Scholar
  77. Hartkamp, N. S., Petersen, E. T., De Vis, J. B., Bokkers, R. P., & Hendrikse, J. (2013). Mapping of cerebral perfusion territories using territorial arterial spin labeling: techniques and clinical application. NMR in Biomedicine, 26(8), 901–912.PubMedCrossRefGoogle Scholar
  78. Hedström, M., Haglund, K., Skolin, I., & Von Essen, L. (2003). Distressing events for children and adolescents with cancer: Child, parent, an nurse perceptions. Journal of pediatric oncology nursing, 20(3), 120–132.PubMedCrossRefGoogle Scholar
  79. 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(1), 102–111.PubMedCrossRefGoogle Scholar
  80. Hill, D. E., Ciesielski, K. T., Hart, B. L., & Jung, R. E. (2004). MRI morphometric and neuropsychological correlates of long-term memory in survivors of childhood leukemia. Pediatric Blood & Cancer, 42(7), 611–617.CrossRefGoogle Scholar
  81. Hobbie, W. L., Ogle, S. K., Reilly, M., Ginsberg, J. P., Rourke, M., Ratcliffe, S., et al. (2010). Identifying the educational needs of parents at the completion of their child’s cancer therapy. Journal of pediatric oncology nursing, 27(4), 190–195.PubMedCrossRefGoogle Scholar
  82. Hopewell, J., Calvo, W., Jaenke, R., Reinhold, H., Robbins, M., & Whitehouse, E. (1993). Microvasculature and radiation damage. In Acute and Long-Term Side-Effects of Radiotherapy (pp. 1–16). Berlin: Springer.Google Scholar
  83. Horska, A., Nidecker, A., Intrapiromkul, J., Tannazi, F., Ardekani, S., Brant, L. J., Wharam Jr., M., et al. (2014). Diffusion tensor imaging of deep gray matter in children treated for brain malignancies. Child's Nervous System, 30, 631–638.Google Scholar
  84. Hosseini, S. H., Hoeft, F., & Kesler, S. R. (2012). GAT: a graph-theoretical analysis toolbox for analyzing between-group differences in large-scale structural and functional brain networks. PloS one, 7(7), e40709.PubMedPubMedCentralCrossRefGoogle Scholar
  85. Howlader, N., Noone, A., Krapcho, M., Miller, D., Bishop, K., Altekruse, S., et al. (2016). SEER Cancer Statistics Review, 1975-2013, National Cancer Institute. Bethesda.Google Scholar
  86. Huang, H., Gundapuneedi, T., & Rao, U. (2012). White matter disruptions in adolescents exposed to childhood maltreatment and vulnerability to psychopathology. Neuropsychopharmacology, 37(12), 2693–2701.PubMedPubMedCentralCrossRefGoogle Scholar
  87. Iyer, N. S., Balsamo, L. M., Bracken, M. B., & Kadan-Lottick, N. S. (2015). Chemotherapy-only treatment effects on long-term neurocognitive functioning in childhood ALL survivors: a review and meta-analysis. Blood, 126(3), 346–353.PubMedCrossRefGoogle Scholar
  88. Jacola, L. M., Ashford, J. M., Reddick, W. E., Glass, J. O., Ogg, R. J., Merchant, T. E., & Conklin, H. M. (2014). The relationship between working memory and cerebral white matter volume in survivors of childhood brain tumors treated with conformal radiation therapy. Journal of Neuro-Oncology, 119, 197–205.Google Scholar
  89. Jayakar, R., King, T. Z., Morris, R., & Na, S. (2015). Hippocampal volume and auditory attention on a verbal memory task with adult survivors of pediatric brain tumor. Neuropsychology, 29(2), 303.PubMedCrossRefGoogle Scholar
  90. Jean-Pierre, P., & McDonald, B. C. (2016). Neuroepidemiology of cancer and treatment-related neurocognitive dysfunction in adult-onset cancer patients and survivors. Handb Clin Neurol, 138, 297–309. Scholar
  91. Jim, H. S., & Jacobsen, P. B. (2008). Posttraumatic stress and posttraumatic growth in cancer survivorship: a review. The Cancer Journal, 14(6), 414–419.PubMedCrossRefGoogle Scholar
  92. Joëls, M., Karst, H., Krugers, H. J., & Lucassen, P. J. (2007). Chronic stress: implications for neuronal morphology, function and neurogenesis. Frontiers in Neuroendocrinology, 28(2), 72–96.PubMedCrossRefGoogle Scholar
  93. Kangas, M. (2013). DSM-5 Trauma and Stress-Related Disorders: Implications for Screening for Cancer-Related Stress. Frontiers in Psychiatry, 4, 122. Scholar
  94. Kavanaugh, B. C., Dupont-Frechette, J. A., Jerskey, B. A., & Holler, K. A. (2017). Neurocognitive deficits in children and adolescents following maltreatment: Neurodevelopmental consequences and neuropsychological implications of traumatic stress. Appl Neuropsychol Child, 6(1), 64–78. Scholar
  95. Kazak, A. E., Barakat, L. P., Alderfer, M., Rourke, M. T., Meeske, K., Gallagher, P. R., et al. (2001). Posttraumatic stress in survivors of childhood cancer and mothers: Development and validation of the Impact of Traumatic Stressors Interview Schedule (ITSIS). Journal of Clinical Psychology in Medical Settings, 8(4), 307–323.CrossRefGoogle Scholar
  96. Kazak, A. E., Alderfer, M., Rourke, M. T., Simms, S., Streisand, R., & Grossman, J. R. (2004). Posttraumatic stress disorder (PTSD) and posttraumatic stress symptoms (PTSS) in families of adolescent childhood cancer survivors. Journal of pediatric psychology, 29(3), 211–219.PubMedCrossRefGoogle Scholar
  97. Kazak, A. E., Kassam-Adams, N., Schneider, S., Zelikovsky, N., Alderfer, M. A., & Rourke, M. (2005). An integrative model of pediatric medical traumatic stress. J Pediatr Psychol, 31(4), 343–355.PubMedCrossRefGoogle Scholar
  98. Keding, T. J., & Herringa, R. J. (2015). Abnormal structure of fear circuitry in pediatric post-traumatic stress disorder. Neuropsychopharmacology, 40(3), 537–545.PubMedCrossRefGoogle Scholar
  99. Kesler, S. R., Tanaka, H., & Koovakkattu, D. (2010). Cognitive reserve and brain volumes in pediatric acute lymphoblastic leukemia. Brain imaging and behavior, 4(3-4), 256–269.PubMedPubMedCentralCrossRefGoogle Scholar
  100. Kesler, S. R., Gugel, M., Pritchard-Berman, M., Lee, C., Kutner, E., Hosseini, S., et al. (2014). Altered resting state functional connectivity in young survivors of acute lymphoblastic leukemia. Pediatric Blood & Cancer, 61(7), 1295–1299.CrossRefGoogle Scholar
  101. Kesler, S. R., Gugel, M., Huston-Warren, E., & Watson, C. (2016). Atypical structural connectome organization and cognitive impairment in young survivors of acute lymphoblastic leukemia. Brain connectivity, 6(4), 273–282.PubMedPubMedCentralCrossRefGoogle Scholar
  102. Kessler, R. C., Berglund, P., Demler, O., Jin, R., Merikangas, K. R., & Walters, E. E. (2005). Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Archives of general psychiatry, 62(6), 593–602.PubMedCrossRefGoogle Scholar
  103. Kessler, R. C., McLaughlin, K. A., Green, J. G., Gruber, M. J., Sampson, N. A., Zaslavsky, A. M., et al. (2010). Childhood adversities and adult psychopathology in the WHO World Mental Health Surveys. The British Journal of Psychiatry, 197(5), 378–385.PubMedPubMedCentralCrossRefGoogle Scholar
  104. Keyes, K. M., Eaton, N. R., Krueger, R. F., McLaughlin, K. A., Wall, M. M., Grant, B. F., et al. (2012). Childhood maltreatment and the structure of common psychiatric disorders. Br J Psychiatry, 200(2), 107–115. Scholar
  105. Khajuria, R. K., Blankenburg, F., Wuithschick, I., Rueckriegel, S., Thomale, U.-W., Mansour, M., et al. (2015). Morphological brain lesions of pediatric cerebellar tumor survivors correlate with inferior neurocognitive function but do not affect health-related quality of life. Child's Nervous System, 31(4), 569–580.PubMedCrossRefGoogle Scholar
  106. Khong, P.-L., Kwong, D. L., Chan, G. C., Sham, J. S., Chan, F.-L., & Ooi, G.-C. (2003). Diffusion-tensor imaging for the detection and quantification of treatment-induced white matter injury in children with medulloblastoma: a pilot study. American Journal of Neuroradiology, 24(4), 734–740.Google Scholar
  107. Khong, P.-L., Leung, L. H., Fung, A. S., Fong, D. Y., Qiu, D., Kwong, D. L., … Chan, G. C. (2006). White matter anisotropy in post-treatment childhood cancer survivors: preliminary evidence of association with neurocognitive function. Journal of Clinical Oncology, 24(6), 884–890.Google Scholar
  108. King, T. Z., Na, S., & Mao, H. (2015a). Neural underpinnings of working memory in adult survivors of childhood brain tumors. Journal of the International Neuropsychological Society, 21(07), 494–505.PubMedCrossRefGoogle Scholar
  109. King, T. Z., Wang, L., & Mao, H. (2015b). Disruption of white matter integrity in adult survivors of childhood brain tumors: correlates with long-term intellectual outcomes. PloS one, 10(7), e0131744.PubMedPubMedCentralCrossRefGoogle Scholar
  110. Kirschen, M. P., Davis-Ratner, M. S., Milner, M. W., Chen, S., Schraedley-Desmond, P., Fisher, P. G., et al. (2008). Verbal memory impairments in children after cerebellar tumor resection. Behavioural neurology, 20(1-2), 39–53.PubMedCrossRefGoogle Scholar
  111. Kohman, R. A., & Rhodes, J. S. (2013). Neurogenesis, inflammation and behavior. Brain, behavior, and immunity, 27, 22–32.PubMedCrossRefGoogle Scholar
  112. Konczak, J., Schoch, B., Dimitrova, A., Gizewski, E., & Timmann, D. (2005). Functional recovery of children and adolescents after cerebellar tumour resection. Brain, 128(6), 1428–1441.PubMedCrossRefGoogle Scholar
  113. Krull, K. R., Sabin, N. D., Reddick, W. E., Zhu, L., Armstrong, G. T., Green, D. M., … Robison, L. L. (2012). Neurocognitive function and CNS integrity in adult survivors of childhood hodgkin lymphoma. Journal of Clinical Oncology, 30(29), 3618–3624.Google Scholar
  114. Krull, K. R., Bhojwani, D., Conklin, H. M., Pei, D., Cheng, C., Reddick, W. E., et al. (2013a). Genetic mediators of neurocognitive outcomes in survivors of childhood acute lymphoblastic leukemia. J Clin Oncol, 31(17), 2182–2188. Scholar
  115. Krull, K. R., Hockenberry, M. J., Miketova, P., Carey, M., & Moore, I. M. (2013b). Chemotherapy-related changes in central nervous system phospholipids and neurocognitive function in childhood acute lymphoblastic leukemia. Leukemia & lymphoma, 54(3), 535–540.CrossRefGoogle Scholar
  116. Krull, K. R., Cheung, Y. T., Liu, W., Fellah, S., Reddick, W. E., Brinkman, T. M., et al. (2016). Chemotherapy pharmacodynamics and neuroimaging and neurocognitive outcomes in long-term survivors of childhood acute lymphoblastic leukemia. Journal of clinical oncology, 34(22), 2644–2653.PubMedPubMedCentralCrossRefGoogle Scholar
  117. Kunin-Batson, A. S., Lu, X., Balsamo, L., Graber, K., Devidas, M., Hunger, S. P., et al. (2016). Prevalence and predictors of anxiety and depression after completion of chemotherapy for childhood acute lymphoblastic leukemia: A prospective longitudinal study. Cancer, 122(10), 1608–1617.PubMedPubMedCentralCrossRefGoogle Scholar
  118. Küper, M., Döring, K., Spangenberg, C., Konczak, J., Gizewski, E., Schoch, B., et al. (2013). Location and restoration of function after cerebellar tumor removal—a longitudinal study of children and adolescents. The. Cerebellum, 12(1), 48–58.PubMedCrossRefGoogle Scholar
  119. Landolt, M. A., Ystrom, E., Sennhauser, F. H., Gnehm, H. E., & Vollrath, M. E. (2012). The mutual prospective influence of child and parental post-traumatic stress symptoms in pediatric patients. Journal of child psychology and psychiatry, and allied disciplines, 53(7), 767–774. PubMedCrossRefGoogle Scholar
  120. LeDoux, J. (2003). The emotional brain, fear, and the amygdala. Cellular and molecular neurobiology, 23(4-5), 727–738.PubMedCrossRefGoogle Scholar
  121. Leung, L. H., Ooi, G.-C., Kwong, D. L., Chan, G. C., Cao, G., & Khong, P.-L. (2004). White-matter diffusion anisotropy after chemo-irradiation: a statistical parametric mapping study and histogram analysis. NeuroImage, 21(1), 261–268.Google Scholar
  122. Levisohn, L., Cronin-Golomb, A., & Schmahmann, J. D. (2000). Neuropsychological consequences of cerebellar tumour resection in children. Brain, 123(5), 1041–1050.PubMedCrossRefGoogle Scholar
  123. Li, M. D., Forkert, N. D., Kundu, P., Ambler, C., Lober, R. M., Burns, T. C., … Fisher, P. G. (2017). Brain perfusion and diffusion abnormalities in children treated for posterior fossa brain tumors. The Journal of Pediatrics, 185, 173–180. e173.Google Scholar
  124. Lisman, J. E., & Grace, A. A. (2005). The Hippocampal-VTA Loop: Controlling the Entry of Information into Long-Term Memory. Neuron, 46(5), 703–713. Scholar
  125. Liu, F., Scantlebury, N., Tabori, U., Bouffet, E., Laughlin, S., Strother, D., … Brière, M.-E. (2014). White matter compromise predicts poor intellectual outcome in survivors of pediatric low-grade glioma.Google Scholar
  126. Lu, Q., Krull, K. R., Leisenring, W., Owen, J. E., Kawashima, T., Tsao, J. C., et al. (2011). Pain in long-term adult survivors of childhood cancers and their siblings: a report from the Childhood Cancer Survivor Study. Pain, 152(11), 2616–2624.PubMedPubMedCentralCrossRefGoogle Scholar
  127. Lucas, T., Wegner, R., Pierce, J., Lumley, M. A., Laurent, H. K., & Granger, D. A. (2017). Perceived discrimination, racial identity, and multisystem stress response to social evaluative threat among African American men and women. Psychosomatic Medicine, 79, 293–305.Google Scholar
  128. Lull, M. E., & Block, M. L. (2010). Microglial activation and chronic neurodegeneration. Neurotherapeutics, 7(4), 354–365.PubMedPubMedCentralCrossRefGoogle Scholar
  129. Mabbott, D. J., Noseworthy, M. D., Bouffet, E., Rockel, C., & Laughlin, S. (2006). Diffusion tensor imaging of white matter after cranial radiation in children for medulloblastoma: correlation with IQ. Neuro-Oncology, 8(3), 244–252.Google Scholar
  130. Mahajan, A., & Jenney, M. E. (2004). The survivors of childhood cancer. In Psychosocial aspects of pediatric oncology (pp. 265–278). Chichester: John Wiley & Sons, Ltd.Google Scholar
  131. Marcoux, S., Drouin, S., Laverdière, C., Alos, N., Andelfinger, G. U., Bertout, L., et al. (2016). The PETALE study: Late adverse effects and biomarkers in childhood acute lymphoblastic leukemia survivors. Pediatric Blood & Cancer.
  132. Maren, S., Phan, K. L., & Liberzon, I. (2013). The contextual brain: implications for fear conditioning, extinction and psychopathology. Nature reviews neuroscience, 14(6), 417–428.PubMedPubMedCentralCrossRefGoogle Scholar
  133. Marusak, H. A., Etkin, A., & Thomason, M. E. (2015a). Disrupted insula-based neural circuit organization and conflict interference in trauma-exposed youth. NeuroImage: Clinical, 8, 516–525.CrossRefGoogle Scholar
  134. Marusak, H. A., Martin, K. R., Etkin, A., & Thomason, M. E. (2015b). Childhood trauma exposure disrupts the automatic regulation of emotional processing. Neuropsychopharmacology, 40(5), 1250–1258.PubMedPubMedCentralCrossRefGoogle Scholar
  135. Marusak, H. A., Kuruvadi, N., Vila, A. M., Shattuck, D. W., Joshi, S. H., Joshi, A. A., et al. (2016). Interactive effects of BDNF Val66Met genotype and trauma on limbic brain anatomy in childhood. European child & adolescent psychiatry, 25(5), 509–518.CrossRefGoogle Scholar
  136. Marusak, H. A., Calhoun, V. D., Brown, S., Crespo, L. M., Sala-Hamrick, K., Gotlib, I. H., et al. (2017a). Dynamic functional connectivity of neurocognitive networks in children. Human brain mapping, 38(1), 97–108. Scholar
  137. Marusak, H. A., Hatfield, J. R. B., Thomason, M. E., & Rabinak, C. A. (2017b). Reduced Ventral Tegmental Area–Hippocampal Connectivity in Children and Adolescents Exposed to Early Threat. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 2(2), 130–137. Scholar
  138. McCrory, E., De Brito, S. A., & Viding, E. (2010). Research review: the neurobiology and genetics of maltreatment and adversity. Journal of child psychology and psychiatry, 51(10), 1079–1095.PubMedCrossRefGoogle Scholar
  139. McCrory, E. J., Gerin, M. I., & Viding, E. (2017). Annual research review: Childhood maltreatment, latent vulnerability and the shift to preventative psychiatry–the contribution of functional brain imaging. Journal of Child Psychology and Psychiatry, 58, 338–357.Google Scholar
  140. McDonnell, G. A., Salley, C. G., Barnett, M., DeRosa, A. P., Werk, R. S., Hourani, A., et al. (2017). Anxiety Among Adolescent Survivors of Pediatric Cancer. Journal of Adolescent Health.
  141. McEvoy, S. D., Lee, A., Poliakov, A., Friedman, S., Shaw, D., Browd, S. R., … Mac Donald, C. L. (2016). Longitudinal cerebellar diffusion tensor imaging changes in posterior fossa syndrome. NeuroImage: Clinical, 12, 582–590.Google Scholar
  142. McLaughlin, K. A. (2016). Future Directions in Childhood Adversity and Youth Psychopathology. J Clin Child Adolesc Psychol, 45(3), 361–382. Scholar
  143. McLaughlin, K. A., Sheridan, M. A., & Lambert, H. K. (2014). Childhood adversity and neural development: deprivation and threat as distinct dimensions of early experience. Neuroscience & Biobehavioral Reviews, 47, 578–591.CrossRefGoogle Scholar
  144. McLaughlin, K. A., Sheridan, M. A., Gold, A. L., Duys, A., Lambert, H. K., Peverill, M., et al. (2016). Maltreatment Exposure, Brain Structure, and Fear Conditioning in Children and Adolescents. Neuropsychopharmacology, 41(8), 1956–1964. Scholar
  145. Medicine, I. o., & Council, N. R. (2006). From Cancer Patient to Cancer Survivor: Lost in Transition. Washington, DC: The National Academies Press.Google Scholar
  146. Meeske, K. A., Patel, S. K., Palmer, S. N., Nelson, M. B., & Parow, A. M. (2007). Factors associated with health-related quality of life in pediatric cancer survivors. Pediatric Blood & Cancer, 49(3), 298–305.CrossRefGoogle Scholar
  147. Menon, V. (2011). Large-scale brain networks and psychopathology: a unifying triple network model. Trends in cognitive sciences, 15(10), 483–506.PubMedCrossRefGoogle Scholar
  148. Monje, M., & Dietrich, J. (2012). Cognitive side effects of cancer therapy demonstrate a functional role for adult neurogenesis. Behavioural brain research, 227(2), 376–379.PubMedCrossRefGoogle Scholar
  149. Monje, M., Thomason, M. E., Rigolo, L., Wang, Y., Waber, D. P., Sallan, S. E., et al. (2013). Functional and structural differences in the hippocampus associated with memory deficits in adult survivors of acute lymphoblastic leukemia. Pediatric Blood & Cancer, 60(2), 293–300.CrossRefGoogle Scholar
  150. Mulhern, R. K., & Butler, R. W. (2004). Review Neurocognitive sequelae of childhood cancers and their treatment. Pediatric Rehabilitation, 7(1), 1–14.Google Scholar
  151. Mulhern, R. K., Reddick, W. E., Palmer, S. L., Glass, J. O., Elkin, T. D., Kun, L. E., … Gajjar, A. (1999). Neurocognitive deficits in medulloblastoma survivors and white matter loss. Annals of Neurology, 46(6), 834–841.Google Scholar
  152. Mulhern, R. K., Palmer, S. L., Reddick, W. E., Glass, J. O., Kun, L. E., Taylor, J., Langston, J., & Gajjar, A. (2001). Risks of young age for selected neurocognitive deficits in medulloblastoma are associated with white matter loss. Journal of clinical oncology, 19(2), 472–479.Google Scholar
  153. Nagel, B. J., Palmer, S. L., Reddick, W. E., Glass, J. O., Helton, K. J., Wu, S., et al. (2004). Abnormal hippocampal development in children with medulloblastoma treated with risk-adapted irradiation. American Journal of Neuroradiology, 25(9), 1575–1582.PubMedGoogle Scholar
  154. Norman, R. E., Byambaa, M., De, R., Butchart, A., Scott, J., & Vos, T. (2012). The long-term health consequences of child physical abuse, emotional abuse, and neglect: a systematic review and meta-analysis. PLoS Med, 9(11), e1001349.PubMedPubMedCentralCrossRefGoogle Scholar
  155. Oancea, S. C., Brinkman, T. M., Ness, K. K., Krull, K. R., Smith, W. A., Srivastava, D. K., et al. (2014). Emotional distress among adult survivors of childhood cancer. Journal of Cancer Survivorship, 8(2), 293–303.PubMedPubMedCentralCrossRefGoogle Scholar
  156. O'Farrell, E., MacKenzie, J., & Collins, B. (2013). Clearing the air: a review of our current understanding of "chemo fog". Curr Oncol Rep, 15(3), 260–269. Scholar
  157. Oh, M. E., Driever, P. H., Khajuria, R. K., Rueckriegel, S. M., Koustenis, E., Bruhn, H., & Thomale, U.-W. (2017). DTI fiber tractography of cerebro-cerebellar pathways and clinical evaluation of ataxia in childhood posterior fossa tumor survivors. Journal of Neuro-Oncology, 131(2), 267–276.Google Scholar
  158. Paakko, E., Harila-Saari, A., Vanionpaa, L., Himanen, S., Pyhtinen, J., & Lanning, M. (2000). White matter changes on MRI during treatment in children with acute lymphoblastic leukemia: correlation with neuropsychological findings. Medical and Pediatric Oncology, 35, 456–461.Google Scholar
  159. Pääkkö, E., Lehtinen, S., Harila‐Saari, A., Ahonen, A., Jauhiainen, J., Torniainen, P., Pyhtinen, J., & Lanning, M. (2003). Perfusion MRI and SPECT of brain after treatment for childhood acute lymphoblastic leukemia. Pediatric Blood & Cancer, 40(2), 88–92.Google Scholar
  160. Palmer, S. L., Reddick, W. E., Glass, J. O., Gajjar, A., Goloubeva, O., & Mulhern, R. K. (2002). Decline in corpus callosum volume among pediatric patients with medulloblastoma: longitudinal MR imaging study. American Journal of Neuroradiology, 23(7), 1088–1094.Google Scholar
  161. Pechtel, P., & Pizzagalli, D. A. (2011). Effects of early life stress on cognitive and affective function: an integrated review of human literature. Psychopharmacology, 214(1), 55–70.PubMedCrossRefGoogle Scholar
  162. Penner, L. A., Dovidio, J. F., Gonzalez, R., Albrecht, T. L., Chapman, R., Foster, T., et al. (2016). The effects of oncologist implicit racial bias in racially discordant oncology interactions. Journal of clinical oncology, 34(24), 2874–2880.PubMedPubMedCentralCrossRefGoogle Scholar
  163. Pessoa, L., & Adolphs, R. (2010). Emotion processing and the amygdala: from a'low road'to'many roads' of evaluating biological significance. Nature reviews neuroscience, 11(11), 773–783.PubMedPubMedCentralCrossRefGoogle Scholar
  164. Peterson, A. M., Harper, F. W. K., Albrecht, T. L., Taub, J. W., Orom, H., Phipps, S., et al. (2014). Parent Caregiver Self-Efficacy and Child Reactions to Pediatric Cancer Treatment Procedures. Journal of pediatric oncology nursing : official journal of the Association of Pediatric Oncology Nurses, 31(1), 18–27. CrossRefGoogle Scholar
  165. Phelps, E. A., & LeDoux, J. E. (2005). Contributions of the amygdala to emotion processing: from animal models to human behavior. Neuron, 48(2), 175–187.PubMedCrossRefGoogle Scholar
  166. Phipps, S., Larson, S., Long, A., & Rai, S. N. (2006). Adaptive style and symptoms of posttraumatic stress in children with cancer and their parents. Journal of pediatric psychology, 31(3), 298–309.PubMedCrossRefGoogle Scholar
  167. Pogany, L., Barr, R. D., Shaw, A., Speechley, K. N., Barrera, M., & Maunsell, E. (2006). Health Status in Survivors of Cancer in Childhood and Adolescence. Quality of Life Research, 15(1), 143–157. Scholar
  168. Porto, L., Preibisch, C., Hattingen, E., Bartels, M., Lehrnbecher, T., Dewitz, R., et al. (2008). Voxel-based morphometry and diffusion-tensor MR imaging of the brain in long-term survivors of childhood leukemia. European radiology, 18(11), 2691.PubMedCrossRefGoogle Scholar
  169. Price, J., Kassam-Adams, N., Alderfer, M. A., Christofferson, J., & Kazak, A. E. (2016). Systematic Review: A Reevaluation and Update of the Integrative (Trajectory) Model of Pediatric Medical Traumatic Stress. J Pediatr Psychol, 41(1), 86–97. Scholar
  170. PTSD, N. C. f. (2016) Accessed 4/25/2016.
  171. Qiu, D., Leung, L. H., Kwong, D. L., Chan, G. C., & Khong, P. L. (2006). Mapping radiation dose distribution on the fractional anisotropy map: applications in the assessment of treatment-induced white matter injury. Neuroimage, 31(1), 109–115. Scholar
  172. Qiu, D., Kwong, D. L., Chan, G. C., Leung, L. H., & Khong, P.-L. (2007). Diffusion tensor magnetic resonance imaging finding of discrepant fractional anisotropy between the frontal and parietal lobes after whole-brain irradiation in childhood medulloblastoma survivors: reflection of regional white matter radiosensitivity? International Journal of Radiation Oncology* Biology* Physics, 69(3), 846–851.Google Scholar
  173. Reddick, W. E., Mulhern, R. K., Elkin, T. D., Glass, J. O., Merchant, T. E., & Langston, J. W. (1998). A hybrid neural network analysis of subtle brain volume differences in children surviving brain tumors. Magnetic Resonance Imaging, 16(4), 413–421.Google Scholar
  174. Reddick, W. E., Russell, J. M., Glass, J. O., Xiong, X., Mulhern, R. K., Langston, J. W., Merchant, T. E., et al. (2000). Subtle white matter volume differences in children treated for medulloblastoma with conventional or reduced dose craniospinal irradiation. Magnetic Resonance Imaging, 18, 787–793.Google Scholar
  175. Reddick, W. E., White, H. A., Glass, J. O., Wheeler, G. C., Thompson, S. J., Gajjar, A., Leigh, L., & Mulhern, R. K. (2003). Developmental model relating white matter volume to neurocognitive deficits in pediatric brain tumor survivors. Cancer, 97(10), 2512–2519.Google Scholar
  176. Reddick, W. E., Glass, J. O., Helton, K. J., Langston, J. W., Li, C. S., & Pui, C. H. (2005a). A quantitative MR imaging assessment of leukoencephalopathy in children treated for acute lymphoblastic leukemia without irradiation. AJNR Am J Neuroradiol, 26(9), 2371–2377.PubMedPubMedCentralGoogle Scholar
  177. Reddick, W. E., Glass, J. O., Helton, K. J., Langston, J. W., Xiong, X., Wu, S., et al. (2005b). Prevalence of leukoencephalopathy in children treated for acute lymphoblastic leukemia with high-dose methotrexate. American Journal of Neuroradiology, 26(5), 1263–1269.PubMedPubMedCentralGoogle Scholar
  178. Reddick, W. E., Shan, Z. Y., Glass, J. O., Helton, S., Xiong, X., Wu, S., … Khan, R. B. (2006). Smaller whitematter volumes are associated with larger deficits in attention and learning among long-term survivors of acute lymphoblastic leukemia. Cancer, 106(4), 941–949.Google Scholar
  179. Reddick, W. E., Glass, J. O., Johnson, D. P., Laningham, F. H., & Pui, C.-H. (2009). Voxel-based analysis of T2 hyperintensities in white matter during treatment of childhood leukemia. American Journal of Neuroradiology, 30(10), 1947–1954.Google Scholar
  180. Riccio, C. A., Sullivan, J. R., & Cohen, M. J. (2010). Neuropsychological assessment and intervention for childhood and adolescent disorders. Hoboken: John Wiley & Sons.Google Scholar
  181. Riem, M. M., Alink, L. R., Out, D., Van Ijzendoorn, M. H., & Bakermans-Kranenburg, M. J. (2015). Beating the brain about abuse: Empirical and meta-analytic studies of the association between maltreatment and hippocampal volume across childhood and adolescence. Development and psychopathology, 27(02), 507-520.Google Scholar
  182. Riggs, L., Bouffet, E., Laughlin, S., Laperriere, N., Liu, F., Skocic, J., et al. (2014). Changes to memory structures in children treated for posterior fossa tumors. Journal of the International Neuropsychological Society, 20(02), 168–180.PubMedCrossRefGoogle Scholar
  183. Robinson, K. E., Livesay, K. L., Campbell, L. K., Scaduto, M., Cannistraci, C. J., Anderson, A. W., et al. (2010). Working memory in survivors of childhood acute lymphocytic leukemia: functional neuroimaging analyses. Pediatric Blood & Cancer, 54(4), 585–590.Google Scholar
  184. Robinson, K. E., Fraley, C. E., Pearson, M. M., Kuttesch, J. F., & Compas, B. E. (2013). Neurocognitive late effects of pediatric brain tumors of the posterior fossa: A quantitative review. Journal of the International Neuropsychological Society, 19(01), 44–53.PubMedCrossRefGoogle Scholar
  185. Robinson, K. E., Pearson, M. M., Cannistraci, C. J., Anderson, A. W., Kuttesch Jr, J. F., Wymer, K., et al. (2014). Neuroimaging of executive function in survivors of pediatric brain tumors and healthy controls. Neuropsychology, 28(5), 791.PubMedCrossRefGoogle Scholar
  186. Robinson, K. E., Pearson, M. M., Cannistraci, C. J., Anderson, A. W., Kuttesch Jr, J. F., Wymer, K., et al. (2015). Functional neuroimaging of working memory in survivors of childhood brain tumors and healthy children: Associations with coping and psychosocial outcomes. Child Neuropsychology, 21(6), 779–802.PubMedCrossRefGoogle Scholar
  187. Robison, L. L., & Hudson, M. M. (2014). Survivors of childhood and adolescent cancer: life-long risks and responsibilities. Nature Reviews Cancer, 14(1), 61–70.PubMedCrossRefGoogle Scholar
  188. Rourke, M. T., & Kazak, A. E. (2005). Psychological aspects of long-term survivorship. In Survivors of childhood and adolescent cancer (pp. 295-304): Springer.Google Scholar
  189. Rueckriegel, S. M., Bruhn, H., Thomale, U. W., & Hernáiz Driever, P. (2015). Cerebral white matter fractional anisotropy and tract volume as measured by MR imaging are associated with impaired cognitive and motor function in pediatric posterior fossa tumor survivors. Pediatric Blood & Cancer, 62(7), 1252–1258.Google Scholar
  190. Saban, K. L., Matthews, H. L., DeVon, H. A., & Janusek, L. W. (2014). Epigenetics and social context: implications for disparity in cardiovascular disease. Aging and disease, 5(5).Google Scholar
  191. Scantlebury, N., Bouffet, E., Laughlin, S., Strother, D., McConnell, D., Hukin, J., … Keene, D. (2016). White matter and information processing speed following treatment with cranial-spinal radiation for pediatric brain tumor. Neuropsychology, 30(4), 425.Google Scholar
  192. Schuitema, I., Deprez, S., Van Hecke, W., Daams, M., Uyttebroeck, A., Sunaert, S., et al. (2013). Accelerated aging, decreased white matter integrity, and associated neuropsychological dysfunction 25 years after pediatric lymphoid malignancies. Journal of clinical oncology, 31(27), 3378–3388.PubMedCrossRefGoogle Scholar
  193. Schulte, F., & Barrera, M. (2010). Social competence in childhood brain tumor survivors: a comprehensive review. Supportive Care in Cancer, 18(12), 1499–1513.PubMedCrossRefGoogle Scholar
  194. Seeley, W. W., Menon, V., Schatzberg, A. F., Keller, J., Glover, G. H., Kenna, H., et al. (2007). Dissociable intrinsic connectivity networks for salience processing and executive control. The Journal of neuroscience, 27(9), 2349–2356.PubMedPubMedCentralCrossRefGoogle Scholar
  195. Shan, Z. Y., Liu, J. Z., Glass, J. O., Gajjar, A., Li, C.-S., & Reddick, W. E. (2006). Quantitative morphologic evaluation of white matter in survivors of childhood medulloblastoma. Magnetic Resonance Imaging, 24(8), 1015–1022.Google Scholar
  196. Sharp, K. M. H., Willard, V. W., Barnes, S., Tillery, R., Long, A., & Phipps, S. (2016). Emotion socialization in the context of childhood cancer: Perceptions of parental support promotes posttraumatic growth. Journal of Pediatric Psychology, 42, 95–103.Google Scholar
  197. Simmonds, D. J., Hallquist, M. N., Asato, M., & Luna, B. (2014). Developmental stages and sex differences of white matter and behavioral development through adolescence: a longitudinal diffusion tensor imaging (DTI) study. Neuroimage, 92, 356–368.PubMedCrossRefGoogle Scholar
  198. Singer, T., Seymour, B., O'doherty, J., Kaube, H., Dolan, R. J., & Frith, C. D. (2004). Empathy for pain involves the affective but not sensory components of pain. Science, 303(5661), 1157–1162.PubMedCrossRefGoogle Scholar
  199. Smibert, E., Anderson, V., Godber, T., & Ekert, H. (1996). Risk factors for intellectual and educational sequelae of cranial irradiation in childhood acute lymphoblastic leukaemia. British Journal of Cancer, 73(6), 825.PubMedPubMedCentralCrossRefGoogle Scholar
  200. Smith, K. S., Berridge, K. C., & Aldridge, J. W. (2011). Disentangling pleasure from incentive salience and learning signals in brain reward circuitry. Proceedings of the National Academy of Sciences, 108(27), E255–E264.CrossRefGoogle Scholar
  201. Smith, K. M., King, T. Z., Jayakar, R., & Morris, R. D. (2014). Reading skill in adult survivors of childhood brain tumor: A theory-based neurocognitive model. Neuropsychology, 28(3), 448.Google Scholar
  202. Sroufe, L. A., Egeland, B., Carlson, E. A., & Collins, W. A. (2005). The Development of the Person: The Minnesota Study of Risk and Adaptation from Birth to Adulthood: Guilford Publications.Google Scholar
  203. Stein, K. D., Syrjala, K. L., & Andrykowski, M. A. (2008). Physical and psychological long-term and late effects of cancer. Cancer, 112(S11), 2577–2592.PubMedCrossRefGoogle Scholar
  204. Stepanikova, I., Bateman, L. B., & Oates, G. R. (2017). Systemic inflammation in midlife: race, socioeconomic status, and perceived discrimination. American journal of preventive medicine, 52(1), S63–S76.PubMedPubMedCentralCrossRefGoogle Scholar
  205. Stuber, M. L., Kazak, A. E., Meeske, K., & Barakat, L. (1998). Is posttraumatic stress a viable model for understanding responses to childhood cancer? Child and Adolescent Psychiatric Clinics of North America, 7, 169–182.Google Scholar
  206. Sullivan, T. P., Fehon, D. C., Andres-Hyman, R. C., Lipschitz, D. S., & Grilo, C. M. (2006). Differential relationships of childhood abuse and neglect subtypes to PTSD symptom clusters among adolescent inpatients. Journal of traumatic stress, 19(2), 229–239.PubMedCrossRefGoogle Scholar
  207. Tamnes, C. K., Zeller, B., Amlien, I. K., Kanellopoulos, A., Andersson, S., Due-Tønnessen, P., … Fjell, A. M. (2015). Cortical surface area and thickness in adult survivors of pediatric acute lymphoblastic leukemia. Pediatric Blood & Cancer, 62(6), 1027–1034.Google Scholar
  208. Tavor, I., Jones, O. P., Mars, R., Smith, S., Behrens, T., & Jbabdi, S. (2016). Task-free MRI predicts individual differences in brain activity during task performance. Science, 352(6282), 216–220.PubMedCrossRefGoogle Scholar
  209. Taylor, J., & Turner, R. J. (2002). Perceived discrimination, social stress, and depression in the transition to adulthood: Racial contrasts. Social Psychology Quarterly, 65, 213–225.Google Scholar
  210. Tedeschi, R. G., & Calhoun, L. G. (1995). Trauma and Transformation: Growing in the Aftermath of Suffering: SAGE Publications.Google Scholar
  211. Teicher, M. H., & Samson, J. A. (2016). Annual Research Review: Enduring neurobiological effects of childhood abuse and neglect. Journal of child Psychology and Psychiatry.Google Scholar
  212. Teicher, M. H., Anderson, C. M., Ohashi, K., & Polcari, A. (2014). Childhood maltreatment: altered network centrality of cingulate, precuneus, temporal pole and insula. Biological psychiatry, 76(4), 297–305.PubMedCrossRefGoogle Scholar
  213. Teicher, M. H., Samson, J. A., Anderson, C. M., & Ohashi, K. (2016). The effects of childhood maltreatment on brain structure, function and connectivity. Nat Rev Neurosci, 17(10), 652–666. Scholar
  214. Thomason, M. E., & Marusak, H. A. (2016). Toward understanding the impact of trauma on the early developing human brain. Neuroscience.
  215. Thomason, M. E., Marusak, H. A., Tocco, M. A., Vila, A. M., McGarragle, O., & Rosenberg, D. R. (2015). Altered amygdala connectivity in urban youth exposed to trauma. Social Cognitive and Affective Neuroscience, 10, 1460–1468.Google Scholar
  216. Tiemeier, H., Lenroot, R. K., Greenstein, D. K., Tran, L., Pierson, R., & Giedd, J. N. (2010). Cerebellum development during childhood and adolescence: a longitudinal morphometric MRI study. Neuroimage, 49(1), 63–70.PubMedCrossRefGoogle Scholar
  217. Trentacosta, C. J., Harper, F. W., Albrecht, T. L., Taub, J. W., Phipps, S., & Penner, L. A. (2016). Pediatric Cancer Patients' Treatment-Related Distress and Longer-Term Anxiety: An Individual Differences Perspective. Journal of Developmental & Behavioral Pediatrics, 37(9), 753–761.CrossRefGoogle Scholar
  218. Uddin, L. Q., Supekar, K. S., Ryali, S., & Menon, V. (2011). Dynamic reconfiguration of structural and functional connectivity across core neurocognitive brain networks with development. The Journal of neuroscience : the official journal of the Society for Neuroscience, 31(50), 18578–18589. CrossRefGoogle Scholar
  219. Uphold, H., Peterson, A., Harper, F. W., Fox, J., Foster, T., Phipps, S., et al. (2013). Basic needs of pediatric oncology patients, families, and their psychosocial adjustment. Journal of Clinical Oncology, 31, e20646.
  220. Witter, M. P. (2010). Connectivity of the hippocampus. In Hippocampal microcircuits (pp. 5-26): Springer.Google Scholar
  221. Wolfe, K. R., Madan-Swain, A., & Kana, R. K. (2012). Executive dysfunction in pediatric posterior fossa tumor survivors: A systematic literature review of neurocognitive deficits and interventions. Developmental neuropsychology, 37(2), 153–175.PubMedPubMedCentralCrossRefGoogle Scholar
  222. Wolfe, K. R., Madan-Swain, A., Hunter, G. R., Reddy, A. T., Baños, J., & Kana, R. K. (2013). An fMRI investigation of working memory and its relationship with cardiorespiratory fitness in pediatric posterior fossa tumor survivors who received cranial radiation therapy. Pediatric Blood & Cancer, 60(4), 669–675.CrossRefGoogle Scholar
  223. Zebrack, B. J., & Chesler, M. A. (2002). Quality of life in childhood cancer survivors. Psycho-Oncology, 11(2), 132–141.PubMedCrossRefGoogle Scholar
  224. Zeller, B., Tamnes, C. K., Kanellopoulos, A., Amlien, I. K., Andersson, S., Due-Tønnessen, P., et al. (2013). Reduced neuroanatomic volumes in long-term survivors of childhood acute lymphoblastic leukemia. Journal of clinical oncology, 31(17), 2078–2085.PubMedCrossRefGoogle Scholar
  225. Zeltzer, L. K., Recklitis, C., Buchbinder, D., Zebrack, B., Casillas, J., Tsao, J. C., et al. (2009). Psychological status in childhood cancer survivors: a report from the Childhood Cancer Survivor Study. Journal of clinical oncology, 27(14), 2396–2404. Scholar
  226. Zhang, Y., Zou, P., Mulhern, R. K., Butler, R. W., Laningham, F. H., & Ogg, R. J. (2008). Brain structural abnormalities in survivors of pediatric posterior fossa brain tumors: a voxel-based morphometry study using free-form deformation. NeuroImage, 42(1), 218–229.Google Scholar
  227. Zhang, W.-N., Chang, S.-H., Guo, L.-Y., Zhang, K.-L., & Wang, J. (2013). The neural correlates of reward-related processing in major depressive disorder: a meta-analysis of functional magnetic resonance imaging studies. Journal of affective disorders, 151(2), 531–539.PubMedCrossRefGoogle Scholar
  228. Zou, P., Mulhern, R. K., Butler, R. W., Li, C.-S., Langston, J. W., & Ogg, R. J. (2005). BOLD responses to visual stimulation in survivors of childhood cancer. Neuroimage, 24(1), 61–69.PubMedCrossRefGoogle Scholar
  229. Zou, P., Li, Y., Conklin, H. M., Mulhern, R. K., Butler, R. W., & Ogg, R. J. (2012). Evidence of change in brain activity among childhood cancer survivors participating in a cognitive remediation program. Archives of clinical neuropsychology, 27(8), 915–929.PubMedPubMedCentralCrossRefGoogle Scholar
  230. Zou, P., Conklin, H. M., Scoggins, M. A., Li, Y., Li, X., Jones, M. M., et al. (2016). Functional MRI in medulloblastoma survivors supports prophylactic reading intervention during tumor treatment. Brain imaging and behavior, 10(1), 258–271.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health SciencesWayne State UniversityDetroitUSA
  2. 2.Population Studies and Disparities Research ProgramKarmanos Cancer InstituteDetroitUSA
  3. 3.Department of Oncology, School of MedicineWayne State UniversityDetroitUSA
  4. 4.Department of Pediatrics, School of MedicineWayne State UniversityDetroitUSA
  5. 5.Children’s Hospital of MichiganDetroitUSA
  6. 6.Kids Kicking CancerSouthfieldUSA
  7. 7.Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health SciencesWayne State UniversityDetroitUSA
  8. 8.Department of Psychiatry and Behavioral Neurosciences, School of MedicineWayne State UniversityDetroitUSA

Personalised recommendations