Accessible Requires Authentication Published by De Gruyter July 4, 2013

Brain structural and functional changes in adolescents with psychiatric disorders

José Javier Miguel-Hidalgo

Abstract

During adolescence, hormonal and neurodevelopmental changes geared to ensuring reproduction and achieving independence are very likely mediated by the growth of neural processes, remodeling of synaptic connections, increased myelination in prefrontal areas and maturation of connecting subcortical areas. These processes, greatly accelerated in adolescence, follow an asynchronous pattern in different brain areas. Neuroimaging research using functional and structural magnetic resonance imaging has produced most of the insights regarding brain structural and functional neuropathology in adolescent psychiatric disorders. In schizophrenia, first episodes during adolescence are linked to greater-than-normal losses in gray matter density and white matter integrity and show a divergence of maturational trajectories from normative neural development in a progression similar to that of adult-onset schizophrenia. Anxiety and mood disorders in adolescence have been linked to abnormally increased activity in the amygdala and ventral prefrontal cortical areas, although some data suggest that neural abnormalities in the amygdala and anxiety maybe particularly more frequent in adolescents than in adults. Alcohol misuse in adolescence results in reduced integrity in the white matter and reduced gray matter density that, given the high intensity of adolescent synaptic and myelin remodeling, may result in persistent and profound changes in circuits supporting memory and emotional and appetitive control. The interaction of persistent changes due to prenatal exposure with the contemporaneous expression of genetic factors and disturbing environmental exposure may be an important factor in the appearance of psychiatric disorders in adolescence. Further progress in understanding adolescent psychopathology will require postmortem research of molecular and cellular determinants in the adolescent brain.


Corresponding author: José Javier Miguel-Hidalgo, PhD, DMSc, Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 N State Street, Jackson, MS 39216, USA

References

1. Sowell ER, Thompson PM, Toga AW. Mapping adolescent brain maturation using structural magnetic resonance imaging. In: Romer D, Walker EF, editors. Adolescent psychopathology and the developing brain: integrating brain and prevention science. Oxford: Oxford University Press, 2007:55–84. Search in Google Scholar

2. Lenroot RK, Giedd JN. Brain development in children and adolescents: insights from anatomical magnetic resonance imaging. Neurosci Biobehav Rev 2006;30:718–29. Search in Google Scholar

3. Asato MR, Terwilliger R, Woo J, Luna B. White matter development in adolescence: a DTI study. Cereb Cortex 2010;20:2122–31. Search in Google Scholar

4. Raichle ME. A brief history of human brain mapping. Trends Neurosci 2009;32:118–26. Search in Google Scholar

5. Heeger DJ, Ress D. What does fMRI tell us about neuronal activity? Nat Rev Neurosci 2002;3:142–51. Search in Google Scholar

6. Yakovlev PI, Lecours AR. The myelogenetic cycles of regional maturation of the brain. In: Minkowski A, editor. Regional development of the brain in early life. Oxford: Blackwell, 1967:3–70. Search in Google Scholar

7. Huttenlocher PR. Synaptic density in human frontal cortex- developmental mental changes and effects of aging. Brain Res 1979;163:195–205. Search in Google Scholar

8. Huttenlocher PR, de Courten C. The development of synapses in striate cortex of man. Hum Neurobiol 1987;6:1–9. Search in Google Scholar

9. Dobbing J, Sands J. Quantitative growth and development of human brain. Arch Dis Child 1973;48:757–67. Search in Google Scholar

10. Dobbing J, Sands J. Comparative aspects of the brain growth spurt. Early Hum Dev 1979;3:79–83. Search in Google Scholar

11. Giedd JN. Structural magnetic resonance imaging of the adolescent brain. Ann NY Acad Sci 2004;1021:77–85. Search in Google Scholar

12. Spear LP. The adolescent brain and age-related behavioral manifestations. Neurosci Biobehav Rev 2000;24:417–63. Search in Google Scholar

13. Blakemore SJ, Choudhury S. Development of the adolescent brain: implications for executive function and social cognition. J Child Psychol Psychiatry 2006;47:296–312. Search in Google Scholar

14. Bourgeois JP, Goldman-Rakic PS, Rakic P. Synaptogenesis in the prefrontal cortex of thesus monkeys. Cereb Cortex 1994;4:78–96. Search in Google Scholar

15. Steinberg L. Cognitive and affective development in adolescence. Trends Cogn Sci 2005;9:69–74. Search in Google Scholar

16. Paus T, Keshavan M, Giedd JN. Why do many psychiatric disorders emerge during adolescence? Nat Rev Neurosci 2008;9:947–57. Search in Google Scholar

17. Giedd JN, Castellanos FX, Rajapakse JC, Vaituzis AC, Rapoport JL. Sexual dimorphism of the developing human brain. ProgNeuropsychopharmacol Biol Psychiatry 1997;21:1185–201. Search in Google Scholar

18. Gogtay N, Thompson PM. Mapping gray matter development: implications for typical development and vulnerability to psychopathology. Brain Cogn 2010;72:6–15. Search in Google Scholar

19. Markham JA, Morris JR, Juraska JM. Neuron number decreases in the rat ventral, but not dorsal, medial prefrontal cortex between adolescence and adulthood. Neuroscience 2007;144:961–8. Search in Google Scholar

20. Sowell ER, Peterson BS, Thompson PM, Welcome SE, Henkenius AL, et al. Mapping cortical change across the human life span. Nat Neurosci 2003;6:309–15. Search in Google Scholar

21. Sowell ER, Thompson PM, Leonard CM, Welcome SE, Kan E, et al. Longitudinal mapping of cortical thickness and brain growth in normal children. J Neurosci 2004;24:8223–31. Search in Google Scholar

22. Yurgelun-Todd D. Emotional and cognitive changes during adolescence. Curr Opin Neurobiol 2007;17:251–7. Search in Google Scholar

23. Herting MM, Maxwell EC, Irvine C, Nagel BJ. The impact of sex, puberty, and hormones on white matter microstructure in adolescents. Cereb Cortex 2012;22:1979–92. Search in Google Scholar

24. Fairchild G, Passamonti L, Hurford G, Hagan CC, von dem Hagen EA, et al. Brain structure abnormalities in early-onset and adolescent-onset conduct disorder. Am J Psychiatry 2011;168:624–33. Search in Google Scholar

25. Sturman DA, Moghaddam B. The neurobiology of adolescence: changes in brain architecture, functional dynamics, and behavioral tendencies. Neurosci Biobehav Rev 2011;35:1704–12. Search in Google Scholar

26. Nelson EE, Leibenluft E, McClure EB, Pine DS. The social re-orientation of adolescence: a neuroscience perspective on the process and its relation to psychopathology. Psychol Med 2005;35:163–74. Search in Google Scholar

27. Ernst M, Pine DS, Hardin M. Triadic model of the neurobiology of motivated behavior in adolescence. Psychol Med 2006;36: 299–312. Search in Google Scholar

28. Pfeifer JH, Masten CL, Moore WE 3rd, Oswald TM, Mazziotta JC, et al. Entering adolescence: resistance to peer influence, risky behavior, and neural changes in emotion reactivity. Neuron 2011;69:1029–36. Search in Google Scholar

29. Forbes EE, Hariri AR, Martin SL, Silk JS, Moyles DL, et al. Altered striatal activation predicting real-world positive affect in adolescent major depressive disorder. Am J Psychiatry 2009;166:64–73. Search in Google Scholar

30. Forbes EE, Ryan ND, Phillips ML, Manuck SB, Worthman CM, et al. Healthy adolescents’ neural response to reward: associations with puberty, positive affect, and depressive symptoms. J Am Acad Child Adolesc Psychiatry 2010;49: 162–72. Search in Google Scholar

31. Chen X, Coles CD, Lynch ME, Hu X. Understanding specific effects of prenatal alcohol exposure on brain structure in young adults. Hum Brain Map 2012;33:1663–76. Search in Google Scholar

32. Barde LH, Yeatman JD, Lee ES, Glover G, Feldman HM. Differences in neural activation between preterm and full term born adolescents on a sentence comprehension task: implications for educational accommodations. Dev Cogn Neurosci 2012;2(Suppl 1):S114–28. Search in Google Scholar

33. Schneider S, Peters J, Bromberg U, Brassen S, Miedl SF, et al. Risk taking and the adolescent reward system: a potential common link to substance abuse. Am J Psychiatry 2012;169: 39–46. Search in Google Scholar

34. Berns GS, Moore S, Capra CM. Adolescent engagement in dangerous behaviors is associated with increased white matter maturity of frontal cortex. PLoS One 2009;4:e6773. Search in Google Scholar

35. Kumra S, Ashtari M, Wu J, Hongwanishkul D, White T, et al. Gray matter volume deficits are associated with motor and attentional impairments in adolescents with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2011;35: 939–43. Search in Google Scholar

36. Ziermans TB, Schothorst PF, Schnack HG, Koolschijn PC, Kahn RS, et al. Progressive structural brain changes during development of psychosis. Schizophr Bull 2012;38:519–30. Search in Google Scholar

37. Douaud G, Mackay C, Andersson J, James S, Quested D, et al. Schizophrenia delays and alters maturation of the brain in adolescence. Brain 2009;132:2437–48. Search in Google Scholar

38. Ziermans TB, Durston S, Sprong M, Nederveen H, van Haren NE, et al. No evidence for structural brain changes in young adolescents at ultra high risk for psychosis. Schizophr Res 2009;112:1–6. Search in Google Scholar

39. Walker EF, Mcmillan A, Mittal V. Neurohormones, neurodevelopment, and the prodrome of psychosis in adolescence. In: Romer D, Walker EF, editors. Adolescent psychopathology and the developing brain: integrating brain and prevention science. Oxford: Oxford University Press, 2007:264–83. Search in Google Scholar

40. Walker EF, Diforio D. Schizophrenia: a neural diathesis-stress model. Psychol Rev 1997;104:667–85. Search in Google Scholar

41. Cunningham MG, Bhattacharyya S, Benes FM. Amygdalo-cortical sprouting continues into early adulthood: implications for the development of normal and abnormal function during adolescence. J Comp Neurol 2002;453:116–30. Search in Google Scholar

42. Wolf OT, Convit A, de Leon MJ, Caraos C, Qadri SF. Basal hypothalamo-pituitary-adrenal axis activity and corticotropin feedback in young and older men: relationships to magnetic resonance imaging-derived hippocampus and cingulate gyrus volumes. Neuroendocrinology 2002;75:241–9. Search in Google Scholar

43. Tessner KD, Walker EF, Dhruv SH, Hochman K, Hamann S. The relation of cortisol levels with hippocampus volumes under baseline and challenge conditions. Brain Res 2007; 1179:70–8. Search in Google Scholar

44. Starkman MN, Giordani B, Gebarski SS, Berent S, Schork MA, et al. Decrease in cortisol reverses human hippocampal atrophy following treatment of Cushing’s disease. Biol Psychiatry 1999;46:1595–602. Search in Google Scholar

45. Lupien SJ, de Leon M, de Santi S, Convit A, Tarshish C, et al. Cortisol levels during human aging predict hippocampal atrophy and memory deficits. Nat Neurosci 1998;1:69–73. Search in Google Scholar

46. Starkman MN, Gebarski SS, Berent S, Schteingart DE. Hippocampal formation volume, memory dysfunction, and cortisol levels in patients with Cushing’s syndrome. Biol Psychiatry 1992;32:756–65. Search in Google Scholar

47. Ryan MC, Sharifi N, Condren R, Thakore JH. Evidence of basal pituitary-adrenal overactivity in first episode, drug naive patients with schizophrenia. Psychoneuroendocrinology 2004;29:1065–70. Search in Google Scholar

48. Steen RG, Mull C, McClure R, Hamer RM, Lieberman JA. Brain volume in first-episode schizophrenia: systematic review and meta-analysis of magnetic resonance imaging studies. Br J Psychiatry 2006;188:510–8. Search in Google Scholar

49. Matsumoto H, Simmons A, Williams S, Pipe R, Murray R, et al. Structural magnetic imaging of the hippocampus in early onset schizophrenia. Biol Psychiatry 2001;49:824–31. Search in Google Scholar

50. Janssen J, Reig S, Aleman Y, Schnack H, Udias JM, et al. Gyral and sulcal cortical thinning in adolescents with first episode early-onset psychosis. Biol Psychiatry 2009;66:1047–54. Search in Google Scholar

51. White T, Kendi AT, Lehericy S, Kendi M, Karatekin C, et al. Disruption of hippocampal connectivity in children and adolescents with schizophrenia--a voxel-based diffusion tensor imaging study. Schizophr Res 2007;90:302–7. Search in Google Scholar

52. Gogtay N, Giedd JN, Lusk L, Hayashi KM, Greenstein D, et al. Dynamic mapping of human cortical development during childhood through early adulthood. Proc Natl Acad Sci USA 2004;101:8174–9. Search in Google Scholar

53. Suzuki M, Hagino H, Nohara S, Zhou SY, Kawasaki Y, et al. Male-specific volume expansion of the human hippocampus during adolescence. Cereb Cortex 2005;15:187–93. Search in Google Scholar

54. Isgor C, Kabbaj M, Akil H, Watson SJ. Delayed effects of chronic variable stress during peripubertal-juvenile period on hippocampal morphology and on cognitive and stress axis functions in rats. Hippocampus 2004;14:636–48. Search in Google Scholar

55. Neumann CS, Grimes K, Walker EF, Baum K. Developmental pathways to schizophrenia: behavioral subtypes. J Abnorm Psychol 1995;104:558–66. Search in Google Scholar

56. McClure EB, Pine DS. Social stress, affect, and neural function in adolescence. In: Romer D, Walker E, editors. Adolescent psychopathology and the developing brain: integrating brain and prevention science. Oxford: Oxford University Press, 2007:219–44. Search in Google Scholar

57. Monk CS, Nelson EE, McClure EB, Mogg K, Bradley BP, et al. Ventrolateral prefrontal cortex activation and attentional bias in response to angry faces in adolescents with generalized anxiety disorder. Am J Psychiatry 2006;163:1091–7. Search in Google Scholar

58. McClure EB, Monk CS, Nelson EE, Parrish JM, Adler A, et al. Abnormal attention modulation of fear circuit function in pediatric generalized anxiety disorder. Arch Gen Psychiatry 2007;64:97–106. Search in Google Scholar

59. Thomas KM, Drevets WC, Dahl RE, Ryan ND, Birmaher B, et al. Amygdala response to fearful faces in anxious and depressed children. Arch Gen Psychiatry 2001;58:1057–63. Search in Google Scholar

60. Casey BJ, Duhoux S, Malter Cohen M. Adolescence: what do transmission, transition, and translation have to do with it? Neuron 2010;67:749–60. Search in Google Scholar

61. Rosso IM, Cintron CM, Steingard RJ, Renshaw PF, Young AD, et al. Amygdala and hippocampus volumes in pediatric major depression. Biol Psychiatry 2005;57:21–6. Search in Google Scholar

62. Monk CS, Klein RG, Telzer EH, Schroth EA, Mannuzza S, et al. Amygdala and nucleus accumbens activation to emotional facial expressions in children and adolescents at risk for major depression. Am J Psychiatry 2008;165:90–8. Search in Google Scholar

63. MacMillan S, Szeszko PR, Moore GJ, Madden R, Lorch E, et al. Increased amygdala: hippocampal volume ratios associated with severity of anxiety in pediatric major depression. J Child Adolesc Psychopharmacol 2003;13:65–73. Search in Google Scholar

64. MacMaster FP, Kusumakar V. Hippocampal volume in early onset depression. BMC Medicine 2004;2:2. Search in Google Scholar

65. Blumberg HP, Martin A, Kaufman J, Leung HC, Skudlarski P, et al. Frontostriatal abnormalities in adolescents with bipolar disorder: preliminary observations from functional MRI. Am J Psychiatry 2003;160:1345–7. Search in Google Scholar

66. Steingard RJ, Renshaw PF, Hennen J, Lenox M, Cintron CB, et al. Smaller frontal lobe white matter volumes in depressed adolescents. Biol Psychiatry 2002;52:413–7. Search in Google Scholar

67. Cullen KR, Klimes-Dougan B, Muetzel R, Mueller BA, Camchong J, et al. Altered white matter microstructure in adolescents with major depression: a preliminary study. J Am Acad Child Adolesc Psychiatry 2010;49:173–83. Search in Google Scholar

68. Cullen KR, Gee DG, Klimes-Dougan B, Gabbay V, Hulvershorn L, et al. A preliminary study of functional connectivity in comorbid adolescent depression. Neurosci Lett 2009;460:227–31. Search in Google Scholar

69. Jin C, Gao C, Chen C, Ma S, Netra R, et al. A preliminary study of the dysregulation of the resting networks in first-episode medication-naive adolescent depression. Neurosci Lett 2011;503:105–9. Search in Google Scholar

70. Pandey GN, Dwivedi Y. Neurobiology of teenage suicide. In: Dwivedi Y, editor. The neurobiological basis of suicide. Boca Raton, FL: Taylor Francis/CRC Press, 2012:315–32. Search in Google Scholar

71. Pandey GN, Dwivedi Y, Rizavi HS, Ren X, Pandey SC, et al. Higher expression of serotonin 5-HT(2A) receptors in the postmortem brains of teenage suicide victims. Am J Psychiatry 2002;159:419–29. Search in Google Scholar

72. Pandey GN, Ren X, Rizavi HS, Conley RR, Roberts RC, et al. Brain-derived neurotrophic factor and tyrosine kinase B receptor signalling in post-mortem brain of teenage suicide victims. Int J Neuropsychopharmacol 2008;11:1047–61. Search in Google Scholar

73. Pandey GN, Dwivedi Y, Ren X, Rizavi HS, Roberts RC, et al. Cyclic AMP response element-binding protein in post-mortem brain of teenage suicide victims: specific decrease in the prefrontal cortex but not the hippocampus. Int J Neuropsychopharmacol 2007;10:621–9. Search in Google Scholar

74. Pandey GN, Rizavi HS, Ren X, Fareed J, Hoppensteadt DA, et al. Proinflammatory cytokines in the prefrontal cortex of teenage suicide victims. J Psychiatr Res 2012;46:57–63. Search in Google Scholar

75. Guerri C, Pascual M. Mechanisms involved in the neurotoxic, cognitive, and neurobehavioral effects of alcohol consumption during adolescence. Alcohol 2010;44:15–26. Search in Google Scholar

76. De Bellis MD, Clark DB, Beers SR, Soloff PH, Boring AM, et al. Hippocampal volume in adolescent-onset alcohol use disorders. Am J Psychiatry 2000;157:737–44. Search in Google Scholar

77. Nagel BJ, Schweinsburg AD, Phan V, Tapert SF. Reduced hippocampal volume among adolescents with alcohol use disorders without psychiatric comorbidity. Psychiatry Res 2005;139:181–90. Search in Google Scholar

78. De Bellis MD, Narasimhan A, Thatcher DL, Keshavan MS, Soloff P, et al. Prefrontal cortex, thalamus, and cerebellar volumes in adolescents and young adults with adolescent-onset alcohol use disorders and comorbid mental disorders. Alcohol Clin Exp Res 2005;29:1590–600. Search in Google Scholar

79. McQueeny T, Schweinsburg BC, Schweinsburg AD, Jacobus J, Bava S, et al. Altered white matter integrity in adolescent binge drinkers. Alcohol Clin Exp Res 2009;33:1278–85. Search in Google Scholar

80. Tapert SF, Schweinsburg AD, Barlett VC, Brown SA, Frank LR, et al. Blood oxygen level dependent response and spatial working memory in adolescents with alcohol use disorders. Alcohol Clin Exp Res 2004;28:1577–86. Search in Google Scholar

81. Markwiese BJ, Acheson SK, Levin ED, Wilson WA, Swartzwelder HS. Differential effects of ethanol on memory in adolescent and adult rats. Alcohol Clin Exp Res 1998;22:416–21. Search in Google Scholar

82. White AM, Swartzwelder HS. Hippocampal function during adolescence: a unique target of ethanol effects. Ann NY Acad Sci 2004;1021:206–20. Search in Google Scholar

83. White AM, Swartzwelder HS. Age-related effects of alcohol on memory and memory-related brain function in adolescents and adults. Recent Dev Alcohol 2005;17:161–76. Search in Google Scholar

84. Crews FT, Braun CJ, Hoplight B, Switzer RC 3rd, Knapp DJ. Binge ethanol consumption causes differential brain damage in young adolescent rats compared with adult rats. Alcohol Clin Exp Res 2000;24:1712–23. Search in Google Scholar

85. Crews FT, Mdzinarishvili A, Kim D, He J, Nixon K. Neurogenesis in adolescent brain is potently inhibited by ethanol. Neuroscience 2006;137:437–45. Search in Google Scholar

86. Li Q, Wilson WA, Swartzwelder HS. Differential effect of ethanol on NMDA EPSCs in pyramidal cells in the posterior cingulate cortex of juvenile and adult rats. J Neurophysiol 2002;87:705–11. Search in Google Scholar

87. Pascual M, Boix J, Felipo V, Guerri C. Repeated alcohol administration during adolescence causes changes in the mesolimbic dopaminergic and glutamatergic systems and promotes alcohol intake in the adult rat. J Neurochem 2009;108:920–31. Search in Google Scholar

88. Pandey SC, Ugale R, Zhang H, Tang L, Prakash A. Brain chromatin remodeling: a novel mechanism of alcoholism. J Neurosci 2008;28:3729–37. Search in Google Scholar

89. Li K, Zhu D, Guo L, Li Z, Lynch ME, et al. Connectomics signatures of prenatal cocaine exposure affected adolescent brains. Hum Brain Mapp 2012; Epub ahead of print. DOI: 10.1002/hbm.22082. Search in Google Scholar

90. Black YD, Maclaren FR, Naydenov AV, Carlezon WA Jr., Baxter MG, et al. Altered attention and prefrontal cortex gene expression in rats after binge-like exposure to cocaine during adolescence. J Neurosci 2006;26:9656–65. Search in Google Scholar

91. Lesch KP, Bengel D, Heils A, Sabol SZ, Greenberg BD, et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 1996;274:1527–31. Search in Google Scholar

92. Munafo MR, Brown SM, Hariri AR. Serotonin transporter (5-HTTLPR) genotype and amygdala activation: a meta-analysis. Biol Psychiatry 2008;63:852–7. Search in Google Scholar

93. Lau JY, Goldman D, Buzas B, Fromm SJ, Guyer AE, et al. Amygdala function and 5-HTT gene variants in adolescent anxiety and major depressive disorder. Biol Psychiatry 2009;65:349–55. Search in Google Scholar

94. Bath KG, Lee FS. Variant BDNF (Val66Met) impact on brain structure and function. Cogn Affect Behav Neurosci 2006; 6:79–85. Search in Google Scholar

95. Chen ZY, Jing D, Bath KG, Ieraci A, Khan T, et al. Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior. Science 2006;314:140–3. Search in Google Scholar

96. Lau JY, Goldman D, Buzas B, Hodgkinson C, Leibenluft E, et al. BDNF gene polymorphism (Val66Met) predicts amygdala and anterior hippocampus responses to emotional faces in anxious and depressed adolescents. Neuroimage 2010;53:952–61. Search in Google Scholar

Received: 2012-8-5
Accepted: 2012-9-28
Published Online: 2013-07-04
Published in Print: 2013-09-01

©2013 by Walter de Gruyter Berlin Boston