Hostname: page-component-cd9895bd7-lnqnp Total loading time: 0 Render date: 2024-12-23T13:09:45.195Z Has data issue: false hasContentIssue false
  • English
  • Français

Functional and clinical insights from neuroimaging studies in childhood-onset schizophrenia

Published online by Cambridge University Press:  03 August 2015

Anna E. Ordóñez ,
Nevin V. Sastry  and
Nitin Gogtay
Anna E. Ordóñez*
Affiliation:
Child Psychiatry Branch, National Institute of Mental Health/NIH, Bethesda, Maryland, USA
Nevin V. Sastry
Affiliation:
Child Psychiatry Branch, National Institute of Mental Health/NIH, Bethesda, Maryland, USA
Nitin Gogtay
Affiliation:
Office of Clinical Research, National Institute of Mental Health/NIH, Bethesda, Maryland, USA
*
*Address for correspondence: Anna E. Ordóñez, MD, MAS, Child Psychiatry Branch, NIMH, NIH, Building 10, Rm 3N202, 10 Center Drive, MSC-1600, Bethesda, MD 20892, USA. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Childhood-onset schizophrenia is a rare pediatric onset psychiatric disorder continuous with and typically more severe than its adult counterpart. Neuroimaging research conducted on this population has revealed similarly severe neural abnormalities. When taken as a whole, neuroimaging research in this population shows generally decreased cortical gray matter coupled with white matter connectivity abnormalities, suggesting an anatomical basis for deficits in executive function. Subcortical abnormalities are pronounced in limbic structures, where volumetric deficits are likely related to social skill deficits, and cerebellar deficits that have been correlated to cognitive abnormalities. Structures relevant to motor processing also show a significant alteration, with volumetric increase in basal ganglia structures likely due to antipsychotic administration. Neuroimaging of this disorder shows an important clinical image of exaggerated cortical loss, altered white matter connectivity, and differences in structural development of subcortical areas during the course of development and provides important background to the disease state.

Keywords

Childhood onset schizophrenianeurodevelopmentneuroimagingreviewschizophrenia
Type
Review Articles
Information
CNS Spectrums , Volume 20 , Special Issue 4: Pediatric Neuroimaging , August 2015 , pp. 442 - 450
Copyright
© Cambridge University Press 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Regier, DA, Narrow, WE, Rae, DS, Manderscheid, RW, Locke, BZ, Goodwin, FK. The de facto US mental and addictive disorders service system: epidemiologic catchment area prospective 1-year prevalence rates of disorders and services. Arch Gen Psychiatry. 1993; 50(2): 85–94.CrossRefGoogle Scholar
2. Driver, DI, Gogtay, N, Rapoport, JL. Childhood onset schizophrenia and early onset schizophrenia spectrum disorders. Child Adolesc Psychiatr Clin N Am. 2013; 22(4): 539–555.CrossRefGoogle ScholarPubMed
3. Rapoport, JL, Gogtay, N. Childhood onset schizophrenia: support for a progressive neurodevelopmental disorder. Int J Dev Neurosci. 2011; 29(3): 251–258.CrossRefGoogle ScholarPubMed
4. Nicolson, R, Rapoport, JL. Childhood-onset schizophrenia: rare but worth studying. Biol Psychiatry. 1999; 46(10): 1418–1428.CrossRefGoogle ScholarPubMed
5. Russell, AT. The clinical presentation of childhood-onset schizophrenia. Schizophr Bull. 1994; 20(4): 631–646.CrossRefGoogle ScholarPubMed
6. Asarnow, RF, Asamen, J, Granholm, E, Sherman, T, Watkins, JM, Williams, ME. Cognitive/neuropsychological studies of children with a schizophrenic disorder. Schizophr Bull. 1994; 20(4): 647–669.CrossRefGoogle ScholarPubMed
7. Moran, ME, Hulshoff Pol, H, Gogtay, N. A family affair: brain abnormalities in siblings of patients with schizophrenia. Brain. 2013; 136(11): 3215–3226.CrossRefGoogle ScholarPubMed
8. Greenstein, D, Lerch, J, Shaw, P, et al. Childhood onset schizophrenia: cortical brain abnormalities as young adults. J Child Psychol Psychiatry. 2006; 47(10): 1003–1012.CrossRefGoogle ScholarPubMed
9. Schreier, HA. Hallucinations in nonpsychotic children: more common than we think? J Am Acad Child Adolesc Psychiatry. 1999; 38(5): 623–625.CrossRefGoogle ScholarPubMed
10. Caplan, R. Thought disorder in childhood. J Am Acad Child Adolesc Psychiatry. 1994; 33(5): 605–615.CrossRefGoogle ScholarPubMed
11. McGee, R, Williams, S, Poulton, R. Hallucinations in nonpsychotic children. J Am Acad Child Adolesc Psychiatry. 2000; 39(1): 12–13.CrossRefGoogle ScholarPubMed
12. Rapoport, JL, Giedd, JN, Gogtay, N. Neurodevelopmental model of schizophrenia: update 2012. Mol Psychiatry. 2012; 17(12): 1228–1238.CrossRefGoogle ScholarPubMed
13. Rapoport, JL, Castellanos, XF, Gogate, N, Janson, K, Kohler, S, Nelson, P. Imaging normal and abnormal brain development: new perspectives for child psychiatry. Aust N Z J Psychiatry. 2001; 35(3): 272–281.CrossRefGoogle ScholarPubMed
14. Arango, C, Moreno, C, Martínez, S, et al. Longitudinal brain changes in early-onset psychosis. Schizophr Bull. 2008; 34(2): 341–353.CrossRefGoogle ScholarPubMed
15. Gogtay, N. Cortical brain development in schizophrenia: insights from neuroimaging studies in childhood-onset schizophrenia. Schizophr Bull. 2008; 34(1): 30–36.CrossRefGoogle ScholarPubMed
16. Gogtay, N, Sporn, A, Clasen, LS, et al. Comparison of progressive cortical gray matter loss in childhood-onsetschizophrenia with that in childhood-onset atypical psychoses. AArch Gen Psychiatry. 2004; 61(1): 17–22.CrossRefGoogle ScholarPubMed
17. Thompson, PM, Vidal, C, Giedd, JN, et al. Mapping adolescent brain change reveals dynamic wave of accelerated gray matter loss in very early-onset schizophrenia. Proc Natl Acad Sci U S A. 2001; 98(20): 11650–11655.CrossRefGoogle ScholarPubMed
18. Gogtay, N, Hua, X, Stidd, R, et al. Delayed white matter growth trajectory in young nonpsychotic siblings of patients with childhood-onset schizophrenia. Arch Gen Psychiatry. 2012; 69(9): 875–884.CrossRefGoogle ScholarPubMed
19. Gogtay, N, Lu, A, Leow, AD, et al. Three-dimensional brain growth abnormalities in childhood-onset schizophrenia visualized by using tensor-based morphometry. Proc Natl Acad Sci U S A. 2008; 105(41): 15979–15984.CrossRefGoogle ScholarPubMed
20. Rapoport, JL, Addington, AM, Frangou, S, Psych, MRC. The neurodevelopmental model of schizophrenia: update 2005. Mol Psychiatry. 2005; 10(5): 434–449.CrossRefGoogle ScholarPubMed
21. Ahn, K, Gotay, N, Andersen, TM, et al. High rate of disease-related copy number variations in childhood onset schizophrenia. Mol Psychiatry. 2014; 19(5): 568–572.CrossRefGoogle ScholarPubMed
22. Asarnow, RF, Forsyth, JK. Genetics of childhood-onset schizophrenia. Child Adolesc Psychiatr Clin N Am. 2013; 22(4): 675–687.CrossRefGoogle ScholarPubMed
23. David, CN, Greenstein, D, Clasen, L, et al. Childhood onset schizophrenia: high rate of visual hallucinations. J Am Acad Child Adolesc Psychiatry. 2011; 50(7): 681–686.CrossRefGoogle ScholarPubMed
24. Wagshal, D, Knowlton, BJ, Cohen, JR, et al. Cognitive correlates of gray matter abnormalities in adolescent siblings of patients with childhood-onset schizophrenia. Schizophr Res. 2015; 161(2–3): 345–350.CrossRefGoogle ScholarPubMed
25. Deakin, J, Lennox, B. Psychotic symptoms in young people warrant urgent referral. Practitioner. 2013; 257(1759): 25–28.Google ScholarPubMed
26. Sprooten, E, Papmeyer, M, Smyth, AM, et al. Cortical thickness in first-episode schizophrenia patients and individuals at high familial risk: a cross-sectional comparison. Schizophr Res. 2013; 151(1–3): 259–264.CrossRefGoogle Scholar
27. Assunção Leme, IB, Gadelha, A, Sato, JR, et al. Is there an association between cortical thickness, age of onset, and duration of illness in schizophrenia? CNS Spectr. 2013; 18(6): 315–321.CrossRefGoogle ScholarPubMed
28. Weisinger, B, Greenstein, D, Mattai, A, et al. Lack of gender influence on cortical and subcortical gray matter development in childhood-onset schizophrenia. Schizophr Bull. 2013; 39(1): 52–58.CrossRefGoogle ScholarPubMed
29. Mattai, AA, Weisinger, B, Greenstein, D, et al. Normalization of cortical gray matter deficits in nonpsychotic siblings of patients with childhood-onset schizophrenia. J Am Acad Child Adolesc Psychiatry. 2011; 50(7): 697–704.CrossRefGoogle ScholarPubMed
30. Lett, TA, Voineskos, AN, Kennedy, JL, Levine, B, Daskalakis, ZJ. Treating working memory deficits in schizophrenia: a review of the neurobiology. Biol Psychiatry. 2014; 75(5): 361–370.CrossRefGoogle ScholarPubMed
31. Rapoport, JL, Giedd, JN, Blumenthal, J, et al. Progressive cortical change during adolescence in childhood-onset schizophrenia: a longitudinal magnetic resonance imaging study. Arch Gen Psychiatry. 1999; 56(7): 649–654.CrossRefGoogle ScholarPubMed
32. Jacobsen, LK, Giedd, JN, Castellanos, FX, et al. Progressive reduction of temporal lobe structures in childhood-onset schizophrenia. Am J Psychiatry. 1998; 155(5): 678–685.CrossRefGoogle ScholarPubMed
33. van Haren, NM, Schnack, HG, Cahn, W, et al. Changes in cortical thickness during the course of illness in schizophrenia. Arch Gen Psychiatry. 2011; 68(9): 871–880.CrossRefGoogle ScholarPubMed
34. Bunk, D, Eggers, C, Klapal, M. Symptom dimensions in the course of childhood-onset schizophrenia. Eur Child Adolesc Psychiatry. 1999; 8(Suppl 1): I29–I35.CrossRefGoogle ScholarPubMed
35. Yildiz, M, Borgwardt, SJ, Berger, GE. Parietal lobes in schizophrenia: do they matter? Schizophr Res Treatment. 2011; 2011 Article 581686.CrossRefGoogle ScholarPubMed
36. Alexander-Bloch, AF, Reiss, PT, Rapoport, J, et al. Abnormal cortical growth in schizophrenia targets normative modules of synchronized development. Biol Psychiatry. 2014; 76(6): 438–446.CrossRefGoogle ScholarPubMed
37. Gogtay, N, Giedd, JN, Lusk, L, et al. Dynamic mapping of human cortical development during childhood through early adulthood. Proc Natl Acad Sci U S A. 2004; 101(21): 8174–8179.CrossRefGoogle ScholarPubMed
38. White, T, Moeller, S, Schmidt, M, Pardo, JV, Olman, C. Evidence for intact local connectivity but disrupted regional function in the occipital lobe in children and adolescents with schizophrenia. Hum Brain Mapp. 2012; 33(8): 1803–1811.CrossRefGoogle ScholarPubMed
39. Wynn, JK, Green, MF, Engel, S, et al. Increased extent of object-selective cortex in schizophrenia. Psychiatry Res. 2008; 164(2): 97–105.CrossRefGoogle ScholarPubMed
40. Alexander-Bloch, AF, Gogtay, N, Meunier, D, et al. Disrupted modularity and local connectivity of brain functional networks in childhood-onset schizophrenia. Front Syst Neurosci. 2010; 4: 147.CrossRefGoogle ScholarPubMed
41. White, T, Nelson, M, Lim, KO. Diffusion tensor imaging in psychiatric disorders. Top Magn Reson Imaging. 2008; 19(2): 97–109.CrossRefGoogle ScholarPubMed
42. Alexander-Bloch, AF, Vértes, PE, Stidd, R, et al. The anatomical distance of functional connections predicts brain network topology in health and schizophrenia. Cereb Cortex. 2013; 23(1): 127–138.CrossRefGoogle ScholarPubMed
43. Liu, Y, Liang, M, Zhou, Y, et al. Disrupted small-world networks in schizophrenia. Brain. 2008; 131(Pt 4): 945–961.CrossRefGoogle ScholarPubMed
44. Alexander-Bloch, A, Lambiotte, R, Roberts, B, Giedd, J, Gogtay, N, Bullmore, E. The discovery of population differences in network community structure: new methods and applications to brain functional networks in schizophrenia. Neuroimage. 2012; 59(4): 3889–3900.CrossRefGoogle Scholar
45. Wylie, KP, Tregellas, JR. The role of the insula in schizophrenia. Schizophr Res. 2010; 123(2–3): 93–104.CrossRefGoogle ScholarPubMed
46. Roiz-Santiáñez, R, Pérez-Iglesias, R, Quintero, C, et al. Insular cortex thinning in first episode schizophrenia patients. Psychiatry Res. 2010; 182(3): 216–222.CrossRefGoogle ScholarPubMed
47. Moran, ME, Weisinger, B, Ludovici, K, et al. At the boundary of the self: the insular cortex in patients with childhood-onset schizophrenia, their healthy siblings, and normal volunteers. Int J Dev Neurosci. 2014; 32: 58–63.CrossRefGoogle ScholarPubMed
48. Olabi, B, Ellison-Wright, I, McIntosh, AM, Wood, SJ, Bullmore, E, Lawrie, SM. Are there progressive brain changes in schizophrenia? A meta-analysis of structural magnetic resonance imaging studies. Biol Psychiatry. 2011; 70(1): 88–96.CrossRefGoogle ScholarPubMed
49. Mehler, C, Warnke, A. Structural brain abnormalities specific to childhood-onset schizophrenia identified by neuroimaging techniques. J Neural Transm. 2002; 109(2): 219–234.CrossRefGoogle ScholarPubMed
50. Juuhl-Langseth, M, Rimol, LM, Rasmussen, Jr IA, et al. Comprehensive segmentation of subcortical brain volumes in early onset schizophrenia reveals limited structural abnormalities. Psychiatry Res. 2012; 203(1): 14–23.CrossRefGoogle ScholarPubMed
51. Sowell, ER, Levitt, J, Thompson, PM, et al. Brain abnormalities in early-onset schizophrenia spectrum disorder observed with statistical parametric mapping of structural magnetic resonance images. Am J Psychiatry. 2000; 157(9): 1475–1484.CrossRefGoogle ScholarPubMed
52. Jacobsen, LK, Giedd, JN, Berquin, PC, et al. Quantitative morphology of the cerebellum and fourth ventricle in childhood-onset schizophrenia. Am J Psychiatry. 1997; 154(12): 1663–1669.CrossRefGoogle ScholarPubMed
53. James, AC, James, S, Smith, DM, Javaloyes, A. Cerebellar, prefrontal cortex, and thalamic volumes over two time points in adolescent-onset schizophrenia. Am J Psychiatry. 2004; 161(6): 1023–1029.CrossRefGoogle ScholarPubMed
54. Rapoport, JL, Giedd, J, Kumra, S, et al. Childhood-onset schizophrenia: progressive ventricular change during adolescence. Arch Gen Psychiatry. 1997; 54(10): 897–903.CrossRefGoogle ScholarPubMed
55. Frazier, JA, Giedd, JN, Hamburger, SD, et al. Brain anatomic magnetic resonance imaging in childhood-onset schizophrenia. Arch Gen Psychiatry. 1996; 53(7): 617–624.CrossRefGoogle ScholarPubMed
56. Kraguljac, NV, White, DM, Reid, MA, Lahti, AC. Increased hippocampal glutamate and volumetric deficits in unmedicated patients with schizophrenia. JAMA Psychiatry. 2013; 70(12): 1294–1302.CrossRefGoogle ScholarPubMed
57. Lipska, BK, Jaskiw, GE, Weinberger, DR. Postpubertal emergence of hyperresponsiveness to stress and to amphetamine after neonatal excitotoxic hippocampal damage: a potential animal model of schizophrenia. Neuropsychopharmacology . 1993; 9(1): 67–75.CrossRefGoogle Scholar
58. Moghaddam, B, Krystal, JH. Capturing the angel in “angel dust”: twenty years of translational neuroscience studies of NMDA receptor antagonists in animals and humans. Schizophr Bull. 2012; 38(5): 942–949.CrossRefGoogle Scholar
59. Mattai, A, Hosanagar, A, Weisinger, B, et al. Hippocampal Volume Development in Healthy Siblings of Childhood-Onset Schizophrenia Patients. Am J Psychiatry. 2011; 168(4): 427–435.CrossRefGoogle ScholarPubMed
60. Weinberger, DR. Cell biology of the hippocampal formation in schizophrenia. Biol Psychiatry. 1999; 45(4): 395–402.CrossRefGoogle ScholarPubMed
61. Smith, GN, Lang, DJ, Kopala, LC, Lapointe, JS, Falkai, P, Honer, WG. Developmental abnormalities of the hippocampus in first-episode schizophrenia. Biol Psychiatry. 2003; 53(7): 555–561.CrossRefGoogle ScholarPubMed
62. Lodge, DJ, Grace, AA. Hippocampal dysfunction and disruption of dopamine system regulation in an animal model of schizophrenia. Neurotox Res. 2008; 14(2–3): 97–104.CrossRefGoogle Scholar
63. Mondelli, V, Pariante, CM, Navari, S, et al. Higher cortisol levels are associated with smaller left hippocampal volume in first-episode psychosis. Schizophr Res. 2010; 119(1–3): 75–78.CrossRefGoogle ScholarPubMed
64. 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(6): 510–518.CrossRefGoogle ScholarPubMed
65. Walker, MA, Highley, JR, Esiri, MM, et al. Estimated neuronal populations and volumes of the hippocampus and its subfields in schizophrenia. Am J Psychiatry. 2002; 159(5): 821–828.CrossRefGoogle ScholarPubMed
66. Csernansky, JG, Wang, L, Jones, D, et al. Hippocampal deformities in schizophrenia characterized by high dimensional brain mapping. Am J Psychiatry. 2002; 159(12): 2000–2006.CrossRefGoogle ScholarPubMed
67. Woodward, ND. The course of neuropsychological impairment and brain structure abnormalities in psychotic disorders. Neuroscience Research In press. DOI: 10.1016/j.neures.2014.08.006.Google Scholar
68. Mattai, A, Hosanagar, A, Weisinger, B, et al. Hippocampal volume development in healthy siblings of childhood-onset schizophrenia patients. Am J Psychiatry. 2011; 168(4): 427–435.CrossRefGoogle ScholarPubMed
69. Nugent Iii, TF, Herman, DH, Ordonez, A, et al. Dynamic mapping of hippocampal development in childhood onset schizophrenia. Schizophr Res. 2007; 90(1–3): 62–70.CrossRefGoogle Scholar
70. Levitt, JG, Blanton, RE, Caplan, R, et al. Medial temporal lobe in childhood-onset schizophrenia. Psychiatry Res. 2001; 108(1): 17–27.CrossRefGoogle ScholarPubMed
71. Jacobsen, LK, Giedd, JN, Vaituzis, AC, et al. Temporal lobe morphology in childhood-onset schizophrenia. Am J Psychiatry. 1996; 153(3): 355–361.Google ScholarPubMed
72. Giedd, JN, Jeffries, NO, Blumenthal, J, et al. Childhood-onset schizophrenia: progressive brain changes during adolescence. Biol Psychiatry. 1999; 46(7): 892–898.CrossRefGoogle ScholarPubMed
73. Johnson, SL, Wang, L, Alpert, KI, et al. Hippocampal shape abnormalities of patients with childhood-onset schizophrenia and their unaffected siblings. J Am Acad Child Adolesc Psychiatry. 2013; 52(5): 527–536.CrossRefGoogle ScholarPubMed
74. Eggers, AE. An explanation of why schizophrenia begins with excitotoxic damage to the hippocampus. Med Hypotheses. 2013; 81(6): 1056–1058.CrossRefGoogle ScholarPubMed
75. Zierhut, KC, Graßmann, R, Kaufmann, J, Steiner, J, Bogerts, B, Schiltz, K. Hippocampal CA1 deformity is related to symptom severity and antipsychotic dosage in schizophrenia. Brain. 2013; 136(3): 804–814.CrossRefGoogle ScholarPubMed
76. Aoyama, F, Iida, J, Inoue, M, et al. Brain imaging in childhood- and adolescence-onset schizophrenia associated with obsessive-compulsive symptoms. Acta Psychiatr Scand. 2000; 102(1): 32–37.CrossRefGoogle ScholarPubMed
77. Naudts, K, Hodgins, S. Schizophrenia and violence: a search for neurobiological correlates. Curr Opin Psychiatry. 2006; 19(5): 533–538.CrossRefGoogle ScholarPubMed
78. Haxby, JV, Hoffman, EA, Gobbini, MI. The distributed human neural system for face perception. Trends Cogn Sci. 2000; 4(6): 223–233.CrossRefGoogle ScholarPubMed
79. Pankow, A, Friedel, E, Sterzer, P, et al. Altered amygdala activation in schizophrenia patients during emotion processing. Schizophr Res. 2013; 150(1): 101–106.CrossRefGoogle ScholarPubMed
80. van Erp, TGM, Greve, DN, Rasmussen, J, et al. A multi-scanner study of subcortical brain volume abnormalities in schizophrenia. Psychiatry Res. 2014; 222(1–2): 10–16.CrossRefGoogle ScholarPubMed
81. Morey, RA, Petty, CM, Xu, Y, et al. A comparison of automated segmentation and manual tracing for quantifying hippocampal and amygdala volumes. Neuroimage. 2009; 45(3): 855–866.CrossRefGoogle ScholarPubMed
82. Komlosi, S, Csukly, G, Stefanics, G, Czigler, I, Bitter, I, Czobor, P. Fearful face recognition in schizophrenia: an electrophysiological study. Schizophrenia Res. 2013; 149(1–3): 135–140.CrossRefGoogle ScholarPubMed
83. Zelikowsky, M, Hersman, S, Chawla, MK, Barnes, CA, Fanselow, MS. Neuronal ensembles in amygdala, hippocampus, and prefrontal cortex track differential components of contextual fear. J Neurosci. 2014; 34(25): 8462–8466.CrossRefGoogle ScholarPubMed
84. Lungu, O, Barakat, M, Laventure, S, et al. The incidence and nature of cerebellar findings in schizophrenia: a quantitative review of fMRI literature. Schizophr Bull. 2013; 39(4): 797–806.CrossRefGoogle ScholarPubMed
85. Andreasen, NC, Paradiso, S, O’Leary, DS. “Cognitive dysmetria” as an integrative theory of schizophrenia: a dysfunction in cortical-subcortical-cerebellar circuitry? Schizophr Bull. 1998; 24(2): 203–218.CrossRefGoogle ScholarPubMed
86. Thomann, PA, Roebel, M, Dos Santos, V, Bachmann, S, Essig, M, Schröder, J. Cerebellar substructures and neurological soft signs in first-episode schizophrenia. Psychiatry Res. 2009; 173(2): 83–87.CrossRefGoogle ScholarPubMed
87. Greenstein, D, Lenroot, R, Clausen, L, et al. Cerebellar development in childhood onset schizophrenia and non-psychotic siblings. Psychiatry Res. 2011; 193(3): 131–137.CrossRefGoogle ScholarPubMed
88. Keller, A, Castellanos, FX, Vaituzis, AC, Jeffries, NO, Giedd, JN, Rapoport, JL. Progressive loss of cerebellar volume in childhood-onset schizophrenia. Am J Psychiatry. 2003; 160(1): 128–133.CrossRefGoogle ScholarPubMed
89. Nopoulos, PC, Ceilley, JW, Gailis, EA, Andreasen, NC. An MRI study of cerebellar vermis morphology in patients with schizophrenia: evidence in support of the cognitive dysmetria concept. Biol Psychiatry. 1999; 46(5): 703–711.CrossRefGoogle ScholarPubMed
90. Puget, S, Boddaert, N, Viguier, D, et al. Injuries to inferior vermis and dentate nuclei predict poor neurological and neuropsychological outcome in children with malignant posterior fossa tumors. Cancer. 2009; 115(6): 1338–1347.CrossRefGoogle ScholarPubMed
91. Steinlin, M. The cerebellum in cognitive processes: supporting studies in children. Cerebellum. 2007; 6(3): 237–241.CrossRefGoogle ScholarPubMed
92. Mostofsky, SH, Mazzocco, MMM, Aakalu, G, Warsofsky, IS, Denckla, MB, Reiss, AL. Decreased cerebellar posterior vermis size in fragile X syndrome: correlation with neurocognitive performance. Neurology. 1998; 50(1): 121–130.CrossRefGoogle ScholarPubMed
93. Wagshal, D, Knowlton, BJ, Cohen, JR, et al. Cognitive correlates of gray matter abnormalities in adolescent siblings of patients with childhood-onset schizophrenia. Schizophr Res. 2015; 161(2–3): 345–350.CrossRefGoogle ScholarPubMed
94. Schiffman, J, Sorensen, HJ, Maeda, J, et al. Childhood motor coordination and adult schizophrenia spectrum disorders. Am J Psychiatry. 2009; 166(9): 1041–1047.CrossRefGoogle ScholarPubMed
95. Macmanus, D, Laurens, KR, Walker, EF, Brasfield, JL, Riaz, M, Hodgins, S. Movement abnormalities and psychotic-like experiences in childhood: markers of developing schizophrenia? Psychol Med. 2012; 42(1): 99–109.CrossRefGoogle ScholarPubMed
96. Kumra, S, Giedd, JN, Vaituzis, AC, et al. Childhood-onset psychotic disorders: magnetic resonance imaging of volumetric differences in brain structure. Am J Psychiatry. 2000; 157(9): 1467–1474.CrossRefGoogle ScholarPubMed
97. Scherk, H, Falkai, P. Effects of antipsychotics on brain structure. Curr Opin Psychiatry. 2006; 19(2): 145–150.CrossRefGoogle ScholarPubMed
98. Ballmaier, M, Toga, AW, Siddarth, P, et al. Thought disorder and nucleus accumbens in childhood: a structural MRI study. Psychiatry Res. 2004; 130(1): 43–55.CrossRefGoogle ScholarPubMed
99. Johnson, SLM, Greenstein, D, Clasen, L, et al. Absence of anatomic corpus callosal abnormalities in childhood-onset schizophrenia patients and healthy siblings. Psychiatry Res. 2013; 211(1): 11–16.CrossRefGoogle ScholarPubMed
100. Keller, A, Jeffries, NO, Blumenthal, J, et al. Corpus callosum development in childhood-onset schizophrenia. Schizophr Res. 2003; 62(1–2): 105–114.CrossRefGoogle ScholarPubMed
101. Jacobsen, LK, Giedd, JN, Rajapakse, JC, et al. Quantitative magnetic resonance imaging of the corpus callosum in childhood onset schizophrenia. Psychiatry Res. 1997; 68(2–3): 77–86.CrossRefGoogle ScholarPubMed
102. Usiskin, SI, Nicolson, ROB, Krasnewich, DM, et al. Velocardiofacial syndrome in childhood-onset schizophrenia. J Am Acad Child Adolesc Psychiatry. 1999; 38(12): 1536–1543.CrossRefGoogle ScholarPubMed
103. Wheeler, AL, Voineskos, AN. A review of structural neuroimaging in schizophrenia: from connectivity to connectomics. Front Hum Neurosci. 2014; 8: 653.CrossRefGoogle ScholarPubMed
104. Clark, K, Narr, KL, O’Neill, J, et al. White matter integrity, language, and childhood onset schizophrenia. Schizophr Res. 2012; 138(2–3): 150–156.CrossRefGoogle ScholarPubMed
105. Borofsky, LA, McNealy, K, Siddarth, P, Wu, KN, Dapretto, M, Caplan, R. Semantic processing and thought disorder in childhood-onset schizophrenia: insights from fMRI. J Neurolinguistics. 2010; 23(3): 204–222.CrossRefGoogle ScholarPubMed
106. Moran, ME, Luscher, ZI, McAdams, H, et al. Comparing fractional anisotropy in patients with childhood-onset schizophrenia, their healthy siblings, and normal volunteers through DTI. Schizophr Bull. 2015; 41(1): 66–73.CrossRefGoogle ScholarPubMed