The authors inform no conflict of interest.

ALTERAÇÕES ESTRUTURAIS E BIOQUÍMICAS EM CRIANÇAS VÍTIMAS DE ABUSO INFANTIL: UMA REVISÃO NARRATIVA

Antonio Frabetti Neto (1)

http://lattes.cnpq.br/8500678103815770 – https://orcid.org/0000-0001-8914-2651

Dra Carmen Galego Miziara (2)

http://lattes.cnpq.br/6916238042273197 – https://orcid.org/0000-0002-4266-0117

Giuliana Soares Patricio (3)

http://lattes.cnpq.br/7153113407658931 – https://orcid.org/0000-0003-0565-1534

Victor Covolo Garcia Sanches(4)

http://lattes.cnpq.br/1459795641317080 – https://orcid.org/0000-0002-7176-1873

Gabriel Medeiros Corrêia Da Silva (5)

http://lattes.cnpq.br/0934664854971480 – https://orcid.org/0000-0002-0687-1136

Eduardo Felipe Rodrigues Koniz (6)

http://lattes.cnpq.br/4824923608662053 – https://orcid.org/0000-0001-5545-3654

(1) FMABC, acadêmico, Santo André-SP, Brasil, autor principal

(2) FMABC, faculdade de medicina, Departamento de Medicina Legal e Perícias Médicas, Santo André-SP, Brasil(orientadora)

(3) FMABC, acadêmico, Santo André-SP, Brasil, Co-autor

(4) FMABC, acadêmico, Santo André-SP, Brasil, Co-autor

(5) FMABC, acadêmico, Santo André-SP, Brasil, Co-autor

(6) FMABC, acadêmico, Santo André-SP, Brasil, Co-autor

Email: netofrabetti@hotmail.com

ABSTRACT

Introduction: Humans are defenseless in the first years of life due to the long period necessary for the complete development of the brain, which is shaped by the environment through the neuroplasticity process, and may undergo negative changes according to disastrous experiences. Abuse/violence and child neglect are acts or omissions of care, respectively, potentially capable of causing physical and/or mental harm, actual or potential, against minors under the age of 18. As Brazil reaches alarming levels of violence and child abuse, according to international data linked to the World Health Organization and nationals originating from the Notifiable Diseases Information System (SINAN), the identification of these victims and the adoption of preventive and therapeutic measures make the role of the doctor in society even more fundamental. Children who are subjected to maltreatment have potential risks of attending with structural and biochemical brain alterations which will have a negative impact, and may even be permanent, distinct intensity and vary according to the patient’s age group. Method: A study was carried out at the FMABC University Center through a narrative literature review in the PubMed database, applying the descriptors ”Child Abuse” and ”Brain Development”, with boleano ”and”. The search time was 2016 to 2022. Thirty-five articles were selected based on the reading of the abstracts of each article and listed in order of relevance. RESULTS: Imaging and population studies allowed the relationship of cases of child abuse with structural, volumetric, biochemical and clinical alterations of patients. Thus, although a mandatory causal effect cannot be traced, the relationship between psychopathology and child abuse is well established. In general, the main structural changes seen in victims of child abuse are the reduction of hippocampus, callous body, anterior cingulate cortex, frontal orbit cortex and dorsolateral prefrontal cortex. Furthermore, alterations in the amygdala, cerebellar vermis and hypothalamus-pituitary-adrenal axis give basis to the main clinics of these patients. Another point to consider is the hypothesis that certain polymorphisms can together determine how malleable a person is for both positive and negative experiences (phenotypic plasticity). In genetically susceptible people, epigenetic changes induced by maltreatment that, in turn, alter brain development trajectories can, in many cases, represent the beginning of a crucial chain of events that lead to psychopathology and risk of substance abuse, for example. Therefore, in a country like Brazil where child violence reaches alarming levels, it is mandatory to elucidate the influence of violence imposed on the phases of neurological development (structural and biochemical) on psychopathologies, substance abuse and the perpetuation of violence. This devastating scenario determines that public intervention policies should be widely discussed, developed and implemented. Physicians are responsible for the warning to act as early as possible in the diagnosis, both in educational, preventive measures and at the same time of the adoption of appropriate drug and non-drug therapies not only at the time of violence, but over time so that it can identify possible deviations and, thus, act appropriately. Conclusion: According to the information presented, we have that combating this abuse in childhood and the proper monitoring of these people may cause a reduction in the presentation of the clinical conditions of psychopathy and antisocial personality disorder, which tend, according to the history of these patients, to present problems of a social nature regarding violence and crime perpetration.

Keywords: Structural Changes, Child Violence, Brain

Bibliographical references

1. Glaser Abuso infantil e negligência e o cérebro – uma revisão. J Psiquiatria Psicológica Infantil. 2000 Jan;41(1):97-116
2. Panzer A. The neuroendocrinological sequelae of stress during brain development: the impact of child abuse and neglect. Afr J Psychiatry (Johannesbg). 2008 Feb;11(1):29-34. doi: 4314/ajpsy.v11i1.30252. PMID: 19582322.
3. Teicher MH, Samson JA, Anderson CM, Ohashi K. The effects of childhood maltreatment on brain structure, function and Nat Rev Neurosci. 2016 Sep 19;17(10):652-66. doi: 10.1038/nrn.2016.111. PMID: 27640984
4. De Bellis A psicobiologia da negligência.Child Maltreatment 2005;10(2):150-172.
5. Kisely, S., Abajobir, AA, Mills, R., Strathearn, L., Clavarino, A., & Najman, JM (2018). ). Maus-tratos infantis e problemas de saúde mental na idade adulta: coorte de nascimentos estudar.O Jornal Britânico de Psiquiatria,1–6.https://doi.org/10.1192/bjp.2018.207.
6. Norman, RE, Byambaa, M., De, R., Butchart, A., Scott, J., & Vos, (2012). As consequências de longo prazo para a saúde do abuso físico infantil, abuso emocional e negligência: Uma revisão sistemática e meta-análise.Medicina PLoS, 9(11), e1001349.https://doi.org/10.1371/journal.pmed.1001349.
7. Braga, T., Cunha, O., & Maia, Â. (2018). O efeito duradouro dos maus-tratos no comportamento antissocial: uma meta-análise de estudos Agressividade e Violência Comportamento, 40, 91-100.https://doi.org/10.1016/j.avb.2018.04.003.
8. Scott, S., Knapp, M., Henderson, J., & Maughan, B. (2001). Custo financeiro da exclusão social: Estudo de acompanhamento de crianças anti-sociais na idade adulta.BMJ, 323(7306), https://doi.org/10.1136/bmj.323.7306.191.
9. Widom, CS (2017). Impacto a longo prazo do abuso e negligência na infância sobre o crime e a violência.Ciência e Prática daPsicologia Clínica, 24(2), 186-202.https://doi.org/ 10.1111/cpsp.12194.
10. Wilson, HW, Stover, CS e Berkowitz, SJ (2009). Revisão de Pesquisa: A relação entre a exposição à violência na infância e o comportamento antissocial juvenil: A revisãometa-analítica.Jornal de Psicologia Infantil e Psiquiatria, 50(7), 769-779.https://doi.org/10.1111/j.1469-7610.2008.01974.x.
11. McCrory, EJ, & Viding, (2015). A teoria da vulnerabilidade latente: Reconceituando a ligação entre maus-tratos na infância e transtorno psiquiátrico. Desenvolvimento e Psicopatologia, 27(2), 493-505.https://doi.org/10.1017/S0954579415000115.
12. Schimmenti, , Di Carlo, G., Passanisi, A., & Caretti, V. (2015). Abuso na infância e traços psicopáticos em uma amostra de agressores violentos.Trauma psicológico Prática e Política de Pesquisa de Teoria, 7(4), 340.
13. Felitti, VJ, Anda, RF, Nordenberg, D., Williamson, DF, Spitz, AM, Edwards, V., … Marks, JS (1998). Relação de abuso infantil e família disfunção para muitas das principais causas de morte em O Estudo de Experiências Adversas na Infância (ACE).American Journal of Preventive Medicine, 14(4), 245-258
14. Finkelhor, , Ormrod, RK, & Turner, HA (2007). Polivitimização e trauma em uma coorte longitudinal nacional.Desenvolvimento e Psicopatologia, 19(01),https:// doi.org/10.1017/S0954579407070083.
15. MacKenzie, MJ, Kotch, JB, & Lee, L.-C. (2011). Rumo a um modelo de risco ecológico cumulativo para a etiologia dos maus-tratos Serviços para crianças e jovens Revisão, 33(9), 638-1647.https://doi.org/10.1016/j.childyouth.2011.04.018.
16. Masten, AS, & Wright, MO (1998). Modelos cumulativos de risco e proteção de maus-tratos infantis.Jornal de agressão, maus-tratos e trauma, 2(1), 7-30.https:// doi.org/10.1300/J146v02n01_02.
17. Dong, M., Anda, RF, Felitti, VJ, Dube, SR, Williamson, DF, Thompson, TJ, … Giles, WH (2004). A inter-relação de múltiplas formas de abuso infantil, negligência e disfunção doméstica.Abuso e Negligência Infantil, 28(7),771-784.https://doi.org/10.1016/j.chiabu.2004.01.008. Enders, CK Charmandari E,KinoT, Souvatzoglou E,Chrousos Estresse pediátrico: mediadores hormonais e desenvolvimento humano.Horm Res. 2003;59(4):161-79

22. Flinn MV.Evolução e ontogenia da resposta ao estresse aos desafios sociais na criança Developmental Review.Vol 26(2) Jun 2006, 138-174.
23. Bandura, A. (1973). Agressão: Uma análise de aprendizagem Oxford, Inglaterra: Prentice-Hall. Bandura, A. (1978). Teoria da aprendizagem social da agressão.O Jornal de Comunicação, 28(3), 12-29.
24. Dodge, KA, Bates, JE, & Pettit, GS (1990). Mecanismos no ciclo de violência.Ciência, 250(4988), 1678-1683.https://doi.org/10.1126/science.2270481.
25. De Bellis, M. D. et al. Brain structures in pediatric maltreatment-related posttraumatic stress disorder: a sociodemographically matched study. Biol. Psychiatry 52, 1066–1078 (200

23. De Bellis, M. D. et al. Developmental traumatology part II: brain Biol. Psychiatry 45, 1271–1284 (1999).
24. Teicher, H. et al. Childhood neglect is associated with reduced corpus callosum area. Biol. Psychiatry 56, 80–85 (2004).
25. Andersen, S. L. et al. Preliminary evidence for sensitive periods in the effect of childhood sexual abuse on regional brain development.Neuropsychiatry Clin. Neurosci. 20, 292–301 (2008).

26. Teicher, H., Samson, J. A., Sheu, Y. S., Polcari, A. & McGreenery, C.
27. Hurtful words: association of exposure to peer verbal abuse with elevated psychiatric symptom scores and corpus callosum abnormalities. Am. J. Psychiatry 167, 1464–1471 (2010)
28. Teicher, M. H. et al. Preliminary evidence for abnormal cortical development in physically and sexually abused children using EEG coherence and Ann. NY Acad. Sci. 821, 160–175 (1997)
29. De Bellis, D. & Keshavan, M. S. Sex differences in brain maturation in maltreatment-related pediatric posttraumatic stress disorder.Neurosci. Biobehav. Rev. 27, 103–117 (2003)

29. Juraska, J. M. & Kopcik, J. R. Sex and environmental influences on the size and ultrastructure of the rat corpus callosum. Brain Res. 450, 1–8 (1988).
30. Teicher, H. Wounds that time won’t heal: the neurobiology of child abuse. Cerebrum 4, 50–67 (2000).
31. Kaplow JB,WidomCS.A idade de início dos maus-tratos infantis prediz resultados de saúde mental a longo J Anorm Psychol 2007;116(1):176-187.
32. Sapolsky, M. Stress, glucocorticoids, and damage to the nervous system: the current state of confusion. Stress 1, 1–19 (1996).
33. Andersen, L. & Teicher, M. H. Delayed effects of early stress on hippocampal development. Neuropsychopharmacology 29, 1988–1993 (2004).
34. Noble KG, Tottenham N, Casey Perspectivas da neurociência sobre disparidades na prontidão escolar e desempenho cognitivo.Future Child. Primavera de 2005;15(1):71-89.
35. Teicher MH, Andersen SL, Polcari A, Anderson CM, Navalta CP, Kim As consequências neurobiológicas do estresse precoce e maus-tratos na infância.Neurosci Biobehav Rev 2003;27(1-2):33-44.
36. Naude H, du Preez CS, Pretorius E. O impacto do abuso infantil como estressor ambiental traumático na plasticidade dainteligência. CARSA 2003;4(2):10-26.

37. Chugani, T. et al. Local brain functional activity following early deprivation: a study of postinstitutionalized Romanian orphans. Neuroimage 14, 1290–1301 (2001).
38. Sheu, S., Polcari, A., Anderson, C. M. & Teicher, M. H. Harsh corporal punishment is associated with increased T2 relaxation time indopamine-rich regions. Neuroimage 53, 412–419 (2010).

39. Dannlowski, U. et al. Limbic scars: long-term consequences of childhood maltreatment revealed by functional and structural magnetic resonance imaging. Psychiatry 71, 286–293 (2012)
40. Edmiston, E. E. et al. Corticostriatal-limbic gray matter morphology in adolescents with self-reported exposure to childhood maltreatment. Arch. Pediatr. Adolesc. Med. 165, 1069–1077 (2011)

41. Baker, M. et al. Impact of early versus late childhood early life stress on brain morphometrics. Brain Imag. Behav. 7, 196–203 (2013).
42. Cohen, A. et al. Early life stress and morphometry of the adult anterior cingulate cortex and caudate nuclei. Biol. Psychiatry 59, 975–982 (2006).
43. Thomaes, K. et al. Reduced anterior cingulate and orbitofrontal volumes in child abuse-related complex PTSD. J. Clin. Psychiatry 71, 1636–1644 (2010).
44. Teicher, H., Anderson, C. M., Ohashi, K. & Polcari, A. Childhood maltreatment: altered network centrality of cingulate, precuneus, temporal pole and insula. Biol. Psychiatry 76, 297–305 (2014).
45. van der Werff, J. et al. Resting-state functional connectivity in adults with childhood emotional maltreatment. Psychol. Med. 43, 1825–1836 (2013).
46. Hanson, J. L. et al. Early stress is associated with alterations in the orbitofrontal cortex: a tensorbased morphometry investigation of brain structure and behavioral risk. Neurosci. 30, 7466–7472 (2010).
47. Gerritsen, L. et al. BDNF Val66Met genotype modulates the effect of childhood adversity on subgenual anterior cingulate cortex volume in healthy subjects. Psychiatry 17, 597–603 (2012).
48. Haber, N. & Knutson, B. The reward circuit: linking primate anatomy and human imaging. Neuropsychopharmacology 35, 4–26 (2010).
49. Takiguchi, S. et al. Ventral striatum dysfunction in children and adolescents with reactive attachment disorder: a functional MRI Study. BJPsych Open 1, 121–128 (2015)

57. Hanson, J. L., Hariri, A. R. & Williamson, D. E. Blunted ventral striatum development in adolescence reflects emotional neglect and predicts depressive Biol. Psychiatry 78, 598–605 (2015).
58. Takiguchi, S. et al. Ventral striatum dysfunction in children and adolescents with reactive attachment disorder: a functional MRI BJPsych Open 1, 121–128 (2015).Mehta, M. A. et al. Hyporesponsive reward anticipation in the basal ganglia following severe institutional deprivation early in life. J. Cogn. Neurosci. 22, 2316–2325 (2010).
59. Boecker, R. et al. Impact of early life adversity on reward processing in young adults: EEG-fMRI results from a prospective study over 25 years. PLoS ONE 9, e104185 (2014).
60. Hanson, J. L. et al. Cumulative stress in childhood is associated with blunted reward-related brain activity in adulthood. Soc. Cogn. Affect. 11, 405–412 (2015).
61. Dillon, D. G. et al. Childhood adversity is associated with left basal ganglia dysfunction during reward anticipation in adulthood. Biol. Psychiatry 66, 206–213 (2009)
62. Sirianni Estresse Psicológico e Processamento da Linguagem em Crianças em Idade Escolar. Revista de Fonoaudiologia e Fonoaudiologia. Vol 28(3) Outono de 2004, 112-121
63. Bremner JD,VythilingamM,Vermetten E,Adil J,Khan S,Nazeer A,Afzal N.Cortisol resposta a um desafio de estresse cognitivo no transtorno de estresse pós-traumático (TEPT) relacionado ao abuso infantil. Psiconeuroendocrinologia.2003Aug;28(6):733-50.
64. Susman EJ.Psicobiologia do comportamento antissocial persistente: Estresse, vulnerabilidades precoces e a hipótese de atenuação.Neurosci Biobehav Rev 2006:30(3):276-389
65. Sapolsky RM, Krey LC, McEwen A neuroendocrinologia do estresse e do envelhecimento: A hipótese da cascata de glicocorticóides. Endocr Rev 1986;7:284-301
66. Blair C. Quão semelhantes são a cognição fluida e a inteligência geral? Uma perspectiva da neurociência do desenvolvimento na cognição fluida como um aspecto da capacidade cognitiva humana.Behav Brain Sci 2006:29(2):109-160.
67. Heide KM, Solomon Biologia, trauma de infância e assassinato: Repensando a justiça. Int J Law Psych 2006:29(3);220-233
68. van den Heuvel, M. P. & Hulshoff Pol, H. E. Exploring the brain network: a review on resting-state fMRI functional Eur. Neuropsychopharmacol. 20, 519–534 (2010).
69. Stevens, F. L., Hurley, R. A. & Taber, K. H. Anterior cingulate cortex: unique role in cognition and emotion. Neuropsychiatry Clin. Neurosci. 23, 121–125 (2011).

63. Ross, A. & Olson, I. R. Social cognition and the anterior temporal lobes. Neuroimage 49, 3452–3462 (2010).
64. Amodio, D. M. & Frith, C. D. Meeting of minds: the medial frontal cortex and social cognition. Rev. Neurosci. 7, 268–277 (2006).
65. Cavanna, E. & Trimble, M. R. The precuneus: a review of its functional anatomy and behavioural correlates. Brain 129, 564–583 (2006).
66. Craig, D. How do you feel — now? The anterior insula and human awareness. Nat. Rev. Neurosci. 10, 59–70 (2009)
67. Tomoda, et al. Exposure to parental verbal abuse is associated with increased gray matter volume in superior temporal gyrus. Neuroimage 54, S280–S286 (2011).

68. Choi, J., Jeong, B., Rohan, M. L., Polcari, A. M. & Teicher, M. H. Preliminary evidence for white matter tract abnormalities in young adults exposed to parental verbal abuse. Psychiatry 65, 227–234 (2009).
69. Bogdan , Williamson, D. E. & Hariri, A. R. Mineralocorticoid receptor Iso/Val (rs5522) genotype moderates the association between previous childhood emotional neglect and amygdala reactivity. Am. J. Psychiatry 169, 515–522 (2012).
70. Tomoda,A., Polcari, A., Anderson, C. M. & Teicher, H. Reduced visual cortex gray matter volume and thickness in young adults who witnessed domestic violence during childhood. PLoS ONE 7, e52528 (2012).
71. Choi Jeong, B., Polcari, A., Rohan, M. L. & Teicher, M. H. Reduced fractional anisotropy in the visual limbic pathway of young adults witnessing domestic violence in childhood. Neuroimage 59, 1071–1079 (2012)

72. Tomoda A, Navalta CP,Polcari A, Sadato N, Teicher M H. Childhood sexual abuse is associated with reduced gray matter volume in visual cortex of young women. Biol. Psychiatry 66, 642–648 (2009).
73. Heim, C. M., Mayberg, H. S., Mletzko, T., Nemeroff, C. B. & Pruessner, C. Decreased cortical representation of genital somatosensory field after childhood sexual abuse. Am. J. Psychiatry 170, 616–623 (2013)

74. Dube, R., Felitti, V. J., Dong, M., Giles, W. H. & Anda, R. F. The impact of adverse childhood experiences on health problems: evidence from four birth cohorts dating back to 1900. Prev. Med. 37, 268–277 (2003).

75. Dube, S. R. et al. Childhood abuse, neglect, and household dysfunction and the risk of illicit drug use: the adverse childhood experiences Pediatrics 111, 564–572 (2003).
76. Anda, R. F. et al. Adverse childhood experiences and prescribed psychotropic medications in Am. J. Prev. Med. 32, 389–394 (2007).
77. Brown, W. et al. Adverse childhood experiences and the risk of premature mortality. Am. J. Prev. Med. 37, 389–396 (2009)
78. Price, H., Kao, H. T., Burgers, D. E., Carpenter, L. L. & Tyrka,
    1. Telomeres and early-life stress: an overview. Biol. Psychiatry 73, 15–23 (2013).
79. Pagliaccio, D. et al. Stress-system genes and life stress predict cortisol levels and amygdala and hippocampal volumes in children. Neuropsychopharmacology 39, 1245–1253 (2014).
80. Walsh, N. D. et al. General and specific effects of early-life psychosocial adversities on adolescent grey matter volume. Neuroimage Clin. 4, 308–318 (2014)
81. White, M. G. et al. FKBP5 and emotional neglect interact to predict individual differences in amygdala reactivity. Genes Brain Behav. 11, 869–878 (2012).

82. Hyman, S. E. How adversity gets under the skin. Neurosci. 12, 241–243 (2009)
83. Perroud, N. et al. Methylation of serotonin receptor 3A in ADHD, borderline personality, and bipolar disorders: link with severity of the disorders and childhood maltreatment. Anxiety 33, 45–55 (2016)

Tags: Alterações estruturais Brain Cérebro Child Violence Structural Changes Violência infantil