Neurobiology and phenotypic expression in early onset schizophrenia

Early Intervention in Psychiatry

Volumn 5, Issue 1, 2011, Pages 3-14

  Vyas, Nora S ^a,b,e   Patel, Neva H ^c   Puri, Basant K ^d,f  

^a NATIONAL INSTITUTE OF MENTAL HEALTH   (United States)

^b Department of Nuclear Medicine ^*  (United Kingdom)

^c KING'S COLLEGE LONDON   (United Kingdom)

^d Radiological Sciences Unit   (United Kingdom)

^e IMPERIAL COLLEGE HEALTHCARE NHS TRUST   (United Kingdom)

^f UNIVERSITY OF LIMERICK   (Ireland)

Author keywords

Adolescence; Cognition; Imaging; Intelligence; Prognosis; Schizophrenia

Indexed keywords

NEUROLEPTIC AGENT;

ATTENTION; BRAIN DISEASE; COGNITIVE DEFECT; DISEASE COURSE; EARLY ONSET SCHIZOPHRENIA; EXECUTIVE FUNCTION; GENETIC DISORDER; GENETIC VARIABILITY; HUMAN; INTELLIGENCE; MEMORY; NEUROBIOLOGY; NEUROIMAGING; ONSET AGE; PATHOPHYSIOLOGY; PHENOMENOLOGY; PHENOTYPE; PRIORITY JOURNAL; REVIEW; SCHIZOPHRENIA; SOCIAL PSYCHOLOGY;

ADOLESCENT; ADULT; AGE OF ONSET; ANTIPSYCHOTIC AGENTS; BRAIN; CHILD; COGNITION DISORDERS; DISEASE PROGRESSION; HUMANS; PHENOTYPE; SCHIZOPHRENIA; SCHIZOPHRENIC PSYCHOLOGY;

EID: 79251534718     PISSN: 17517885     EISSN: 17517893     Source Type: Journal    
DOI: 10.1111/j.1751-7893.2010.00253.x     Document Type: Review

References (151)

1. Murray CJ, Lopez AD. The Global Burden of Disease: A Comprehensive Assessment of Mortality and Disability from Diseases, Injuries and Risk Factors in 1990 and Projected to 2020. Boston: Harvard School of Public Health, 1996.
2. Ayuso-Mateos JL. Global Burden of Schizophrenia in the Year 2000 [Global Burden of Disease working paper]. Geneva: WHO, 2006. [Cited 4 Jan 2010.] Available from URL.
3. World Health Organization. World Health Report 2001. Mental Health: New Understanding, New Hope. Geneva: World Health Organization, 2001.
4. Freedman R. Schizophrenia. N Engl J Med 2003; 349: 1738-49.
5. Thomsen PH. Schizophrenia with childhood and adolescent onset - a nationwide register-based study. Acta Psychiatr Scand 1996; 94: 187-93.
6. Huttenlocher PR, Dabholkar AS. Regional differences in synaptogenesis in human cerebral cortex. J Comp Neurol 1997; 387: 167-78.
7. Chugani HT. A critical period of brain development: studies of cerebral glucose utilization with PET. Prev Med 1998; 27: 184-8.
8. Hafner H, Maurer K, Loffler W, Riecher-Rossler A. The influence of age and sex on the onset and early course of schizophrenia. Br J Psychiatry 1993; 162: 80-6.
9. Hafner H, Nowotny B. Epidemiology of early-onset schizophrenia. Eur Arch Psychiatry Clin Neurosci 1995; 245: 80-92.
10. Cannon M, Jones P, Huttunen MO etal. School performance in Finnish children and later development of schizophrenia: a population-based longitudinal study. Arch Gen Psychiatry 1999; 56: 457-63.
11. Galdos PM, van Os JJ, Murray RM. Puberty and the onset of psychosis. Schizophr Res 1993; 10: 7-14.
12. Lewine RR. Comments on 'Puberty and the onset of psychosis' by P.M. Glados etal. Schizophr Res 1994; 13: 81-3.
13. Hollis C. Child and adolescent (juvenile onset) schizophrenia. A case control study of premorbid developmental impairments. Br J Psychiatry 1995; 166: 489-95.
14. Frazier JA, Alaghband-Rad J, Jacobsen L etal. Pubertal development and onset of psychosis in childhood onset schizophrenia. Psychiatry Res 1997; 70: 1-7.
15. Russell AT, Bott L, Sammons C. The phenomenology of schizophrenia occurring in childhood. J Am Acad Child Adolesc Psychiatry 1989; 28: 399-407.
16. Green WH, Padron-Gayol M, Hardesty AS, Bassiri M. Schizophrenia with childhood onset: a phenomenoloy study of 38 cases. J Am Acad Child Adolesc Psychiatry 1992; 31: 968-76.
17. Spencer EK, Campbell M. Children with schizophrenia: diagnosis, phenomenology and pharmacotherapy. Schizophr Bull 1994; 20: 713-25.
18. Gordon CT, Frazier JA, McKenna K, Giedd J, Zametkin A, Zahn T. Childhood-onset schizophrenia: an NIMH study in progress. Schizophr Bull 1994; 20: 697-712.
19. Werry JS, McClellan JM, Andrews LK, Ham M. Clinical features and outcome of child and adolescent schizophrenia. Schizophr Bull 1994; 20: 619-30.
20. Hollis C. Adult outcomes of child- and adolescent-onset schizophrenia: diagnostic stability and predictive validity. Am J Psychiatry 2000; 157: 1652-9.
21. Castle DJ, Murray R. The neurodevelopment basis of sex differences in schizophrenia. Psychol Med 1991; 21: 565-75.
22. McGrath JJ. The surprisingly rich contours of schizophrenia epidemiology. Arch Gen Psychiatry 2007; 25: 55-6.
23. Aleman A, Kahn RS, Selten JP. Sex differences in the risk of schizophrenia: evidence from meta-analysis. Arch Gen Psychiatry 2003; 60: 565-71.
24. McGrath J, Saha S, Welham J, El Saadi O, MacCauley C, Chant D. A systematic review of the incidence of schizophrenia: the distribution of rates and the influence of sex, urbanicity, migrant status and methodology. BMC Med 2004; 2: 13.
25. Remschmidt HE, Schulz E, Martin M, Warnke A, Trott GE. Childhood-onset schizophrenia: history of the concept and recent studies. Schizophr Bull 1994; 20: 727-45.
26. Russell AT. The clinical presentation of childhood-onset schizophrenia. Schizophr Bull 1994; 20: 631-46.
27. Hollis C. Developmental precursors of child- and adolescent-onset schizophrenia and affective psychoses: diagnostic specificity and continuity with symptom dimensions. Br J Psychiatry 2003; 182: 37-44.
28. Remschmidt H, Martin M, Fleischhaker C etal. Forty-two-years later: the outcome of childhood-onset schizophrenia. J Neural Transm 2007; 114: 505-12.
29. Jacobsen LK, Rapoport JL. Research update: childhood-onset schizophrenia: implications of clinical and neurobiological research. J Child Psychol Psychiatry 1998; 39: 101-13.
30. Werry JS, McClellan JM, Chard L. Childhood and adolescent schizophrenic, bipolar, and schizoaffective disorders: a clinical and outcome study. J Am Acad Child Adolesc Psychiatry 1991; 30: 457-65.
31. Asarnow JR, Tompson MC, Goldstein MJ. Childhood-onset schizophrenia: a follow-up study. Schizophr Bull 1994; 20: 599-617.
32. McClellan J, McCurry C. Early onset psychotic disorders: diagnostic stability and clinical characteristics. Eur Child Adolesc Psychiatry 1999; 8: 13-9.
33. Nicolson R, Lenane M, Hamburger SD, Fernandez T, Bedwell J, Rapoport JL. Lessons from childhood-onset schizophrenia. Brain Res Rev 2000a; 31: 147-56.
34. Singh SP. Transition of care from child to adult mental health services: the great divide. Curr Opin Psychiatry 2009; 22: 386-90.
35. Kolvin I. Studies in the childhood psychoses. I. Diagnostic criteria and classification. Br J Psychiatry 1971; 118: 381-4.
36. Kolvin I, Ounsted C, Humphrey M, McNay A. Studies in the childhood psychoses. II. The phenomenology of childhood psychoses. Br J Psychiatry 1971; 118: 385-95.
37. Eggers C. Course and prognosis in childhood schizophrenia. J Autism Child Schizophr 1978; 8: 21-36.
38. Asarnow JR, Ben-Meir S. Children with schizophrenia spectrum and depressive disorders: a comparative study of premorbid adjustment, onset pattern and severity of impairment. J Child Psychol Psychiatry 1988; 29: 477-88.
39. Alaghband-Rad J, McKenna K, Gordon CT etal. Childhood-onset schizophrenia: the severity of premorbid course. J Am Acad Child Adolesc Psychiatry 1995; 34: 1273-83.
40. Green WH, Campbell M, Hardesty AS etal. A comparison of schizophrenic and autistic children. J Am Acad Child Psychiatry 1984; 23: 399-409.
41. Vourdas A, Pipe R, Corrigall R, Frangou S. Increased developmental deviance and premorbid dysfunction in early onset schizophrenia. Schizophr Res 2003; 62: 13-22.
42. Rutter M. Childhood schizophenia reconsidered. J Autism Child Schizophr 1972; 2: 315-37.
43. Bleuler E. (Translated by Zinken J). Dementia Praecox or the Group of Schizophrenias. New York: International Universities Press, 1950.
44. Gerralda ME. Hallucinations in chlidren with conduct and emotional disorders. I. The clinical phenomenia. Psychol Med 1984; 14: 589-96.
45. Cannon TD, Bearden CE, Hollister JM, Rosso IM, Sanchez LE, Hadley T. Childhood cognitive functioning in schizophrenia patients and their unaffected siblings: a prospective cohort study. Schizophr Bull 2000; 26: 379-93.
46. Walker EF, Savoie T, Davis D. Neuromotor precursors of schizophrenia. Schizophr Bull 1994; 20: 441-51.
47. Nicolson R, Lenane M, Singaracharlu S etal. Premorbid speech and language impairments in childhood-onset schizophrenia: association with risk factors. Am J Psychiatry 2000; 157: 794-800.
48. Fleischhaker C, Schulz E, Tepper K, Martin M, Hennighausen K, Remschmidt H. Long-term course of adolescent schizophrenia. Schizophr Bull 2005; 31: 769-80.
49. Watkins JM, Asarnow RF, Tanguay PE. Symptom development in childhood onset schizophrenia. J Child Psychol Psychiatry 1988; 29: 865-78.
50. Schothorst PF, Emck C, van Engeland H. Characteristics of early psychosis. Compr Psychiatry 2006; 47: 438-42.
51. McClellan J, Breiger D, McCurry C, Hlastala SA. Premorbid functioning in early-onset psychotic disorders. J Am Acad Child Adolesc Psychiatry 2003; 42: 666-72.
52. Vyas NS, Hadjulis M, Vourdas A, Byrne P, Frangou S. The Maudsley Early Onset Schizophrenia Study. Predictors of psychosocial outcome at 4-year follow-up. Eur Child Adolesc Psychiatry 2007; 16: 465-70.
53. Done DJ, Crow TJ, Johnstone EC, Sacker A. Childhood antecedents of schizophrenia and affective illness: social adjustment at ages 7 and 11. BMJ 1994; 309: 699-703.
54. Jones P, Rodgers B, Murray R, Marmot M. Child development risk factors for adult schizophrenia in the British 1946 birth cohort. Lancet 1994; 344: 1398-402.
55. Malmberg A, Lewis G, David A, Allebeck P. Premorbid adjustment and personality in people with schizophrenia. Br J Psychiatry 1998; 172: 308-13.
56. Kydd RR, Werry JS. Schizophrenia in children under 16years. J Autism Dev Disord 1982; 12: 343-57.
57. Werry JS, McClellan JM. Predicting outcome in child and adolescent (early onset) schizophrenia and bipolar disorder. J Am Acad Child Adolesc Psychiatry 1992; 31: 147-50.
58. Schmidt M, Blanz B, Dippe A, Koppe T, Lay B. Course of patients diagnosed as having schizophrenia during first episode occurring under age 18years. Eur Arch Psychiatry Clin Neurosci 1995; 245: 93-100.
59. Maziade M, Bouchard S, Gingras N etal. Long term stability of diagnosis and symptom dimensions in a systematic sample of patients with onset of schizophrenia in childhood and early adolescence. II: positive/negative distinction and childhood predictors of adult outcome. Br J Psychiatry 2006; 169: 371-8.
60. Isele R, Merz J, Malzacher M, Angst J. Social disability in schizophrenia: the controlled prospective Burgholzli study II. Premorbid living situation and social adjustment - comparison with a normal control sample. Eur Arch Psychiatry Neurol Sci 1985; 234: 348-56.
61. Eggers C, Bunk D. The long-term course of childhood-onset schizophrenia: a 42-year follow up. Schizophr Bull 1997; 23: 105-17.
62. Reichert A, Kreiker S, Mehler-Wex C, Warnke A. The psychopathological and psychosocial outcome of early-onset schizophrenia: preliminary data on a 13-year follow-up. Child Adolesc Psychiatry Ment Health 2008; 2: 6.
63. Bailer J, Bräuer W, Rey ER. Premorbid adjustment as predictor of outcome in schizophrenia: results of a prospective study. Acta Psychiatr Scand 1996; 93: 368-77.
64. Perkins DO, Gu H, Boteva K, Lieberman JA. Relationship between duration of untreated psychosis and outcome in first-episode schizophrenia: a critical review and meta-analysis. Am J Psychiatry 2005; 162: 1785-804.
65. Bottlender R, Sato T, Jäger M etal. The impact of the duration of untreated psychosis prior to first psychiatric admission on the 15-year outcome in schizophrenia. Schizophr Res 2003; 62: 37-44.
66. Malla AK, Norman RM, Manchanda R etal. One year outcome in first episode psychosis: influence of DUP and other predictors. Schizophr Res 2002; 54: 231-42.
67. Asarnow RF, Asamen J, Grabholm E, Sherman T, Watkins JM, Williams ME. Cognitive/neuropychological studies of children with a schizophrenic disorder. Schizophr Bull 1994; 20: 647-69.
68. Kenny JT, Friedman L, Findling RL etal. Cognitive impairment in adolescents with schizophrenia. Am J Psychiatry 1997; 154: 1613-15.
69. Kumra S, Wiggs E, Bedwell J etal. Neuropsychological deficits in pediatric patients with childhood-onset schizophrenia and psychotic disorders not otherwise specified. Schizophr Res 2000; 42: 135-44.
70. Kravariti E, Morris RG, Rabe-Hesketh S, Murray RM, Frangou S. The Maudsley early onset schizophrenia study: cognitive function in adolescents with recent onset schizophrenia. Schizophr Res 2003a; 61: 137-48.
71. Kravariti E, Morris RG, Rabe-Hesketh S, Murray RM, Frangou S. The Maudsley Early-Onset Schizophrenia Study: cognitive function in adolescent-onset schizophrenia. Schizophr Res 2003b; 65: 95-103.
72. Roofeh D, Cottone J, Burdick KE etal. Deficits in memory strategy use are related to verbal memory impairments in adolescents with schizophrenia-spectrum disorders. Schizophr Res 2006; 85: 201-12.
73. Cervellione KL, Burdick KE, Cottone JG, Rhinewine JP, Kumra S. Neurocognitive deficits in adolescents with schizophrenia: longitudinal stability and predictive utility for short-term functional outcome. J Am Acad Child Adolesc Psychiatry 2007; 46: 867-78.
74. Banaschewski T, Schulz E, Martin M, Remschmidt H. Cognitive functions and psychopathological symptoms in early-onset schizophrenia. Eur Child Adolesc Psychiatry 2000; 9: 11-20.
75. Goldberg TE, Karson GN, Leleszi JP etal. Intellectual impairment in adolescent psychosis: a controlled psychometric study. Schizophr Res 1988; 1: 261-6.
76. Hollis C. Adolescent schizophrenia. Adv Psychiatr Treat 2000; 6: 83-92.
77. David AS, Malmberg A, Brandt L, Allebeck P, Lewis G. IQ and risk for schizophrenia: a population-based cohort study. Psychol Med 1997; 27: 1311-23.
78. Davidson M, Reichenberg A, Rabinowitz J, Weiser M, Kaplan Z, Mark M. Behavioral and intellectual markers for schizophrenia in apparently healthy male adolescents. Am J Psychiatry 1999; 156: 1328-35.
79. Isohanni J, Jarvelin MR, Jones P, Jokelainen J, Isohanni M. Can excellent school performance be a precursor of schizophrenia? A 28-year follow-up in the Northern Finland 1966 birth cohort. Acta Psychiatr Scand 1999; 100: 17-26.
80. Fagerlund B, Pagsberg AK, Hemmingsen RP. Cognitive deficits and levels of IQ in adolescent onset schizophrenia and other psychotic disorders. Schizophr Res 2006; 85: 30-9.
81. Bedwell JS, Keller B, Smith AK, Hamburger S, Kumra S, Rapoport JL. Why does postpsychotic IQ decline in childhood-onset schizophrenia? Am J Psychiatry 1999; 156: 1996-7.
82. Gochman PA, Greenstein D, Sporn A etal. IQ stabilization in childhood-onset schizophrenia. Schizophr Res 2005; 77: 271-7.
83. Biswas P, Malhotra S, Malhotra A, Gupta N. Comparative study of neuropsychological correlates in schizophrenia with onset in childhood, adolescence and adulthood. Eur Child Adolesc Psychiatry 2006; 15: 360-6.
84. White T, Ho BC, Ward J, O'Leary D, Andreasen NC. Neuropsychological performance in first-episode adolescents with schizophrenia: a comparison with first-episode adults and adolescent control subjects. Biol Psychiatry 2006; 60: 463-71.
85. Kravariti E, Morris RG, Rabe-Hesketh S, Murray RM, Frangou S. Comparative profile analysis of cognitive function in recent-onset and chronic patients with adolescent-onset schizophrenia. Schizophr Res 2007; 94: 240-4.
86. Heinrichs RW, Zakzanis KK. Neurocognitive deficit in schizophrenia: a quantitative review of the evidence. Neuropsychology 1998; 12: 426-45.
87. Øie M, Rund BR. Neuropsychological deficits in adolescent-onset schizophrenia compared with attention deficit hyperactivity disorder. Am J Psychiatry 1999; 156: 1216-22.
88. Ueland T, Øie M, Inge Landrø N, Rund BR. Cognitive functioning in adolescents with schizophrenia spectrum disorders. Psychiatry Res 2004; 126: 229-39.
89. Saykin AJ, Shtasel DL, Gur RE etal. Neuropsychological deficits in neuroleptic naive patients with first-episode schizophrenia. Arch Gen Psychiatry 1994; 51: 124-31.
90. Albus M, Hubmann W, Mohr F etal. Are there gender differences in neuropsychological performance in patients with first-episode schizophrenia? Schizophr Res 1997; 28: 39-50.
91. Bilder RM, Goldman RS, Robinson D etal. Neuropsychology of first-episode schizophrenia: initial characterization and clinical correlates. Am J Psychiatry 2000; 157: 549-59.
92. Rhinewine JP, Lencz T, Thaden EP etal. Neurocognitive profile in adolescents with early-onset schizophrenia: clinical correlates. Biol Psychiatry 2005; 58: 705-12.
93. Øie M, Sundet K, Rund BR. Contrasts in memory functions between adolescents with schizophrenia or ADHD. Neuropsychologia 1999; 37: 1351-8.
94. Øie M, Rund BR, Sundet K. Covert visual attention in patients with early-onset schizophrenia. Schizophr Res 1998; 34: 195-205.
95. Rund BR, Zeiner P, Sundet K, Øie M, Bryhn G. No vigilance deficit found in young schizophrenic or ADHD subjects. Scand J Psychol 1998; 39: 101-7.
96. Velligan DI, Bow-Thomas CC. Executive function in schizophrenia. Semin Clin Neuropsychiatry 1999; 4: 24-33.
97. Brickman AM, Buchsbaum MS, Bloom R etal. Neuropsychological functioning in first-break, never-medicated adolescents with psychosis. J Nerv Ment Dis 2004; 192: 615-22.
98. Serper MR, Davidson M, Harvey PD. Attentional predictors of clinical change during neuroleptic treatment in schizophrenia. Schizophr Res 1994; 13: 65-71.
99. Himelhoch S, Taylor SF, Goldman RS, Tandon R. Frontal lobe tasks, antipsychotic medication, and schizophrenia syndromes. Biol Psychiatry 1996; 39: 227-9.
100. Earnst KS, Taylor SF, Smet IC, Goldman RS, Tandon R, Berent S. The effects of typical antipsychotics, clozapine, and risperidone on neuropsychological test performance in schizophrenia. Schizophr Res 1999; 40: 255-6.
101. Keefe RS, Silva SG, Perkins DO, Lieberman JA. The effects of atypical antipsychotic drugs on neurocognitive impairment in schizophrenia: a review and meta-analysis. Schizophr Bull 1999; 25: 201-22.
102. Mishara AL, Goldberg TE. A meta-analysis and critical review of the effects of conventional neuroleptic treatment on cognition in schizophrenia: opening a closed book. Biol Psychiatry 2004; 55: 1013-22.
103. Kallman FJ, Roth B. Genetic aspects of preadolescent schizophrenia. Am J Psychiatry 1956; 112: 599-606.
104. Childs B, Scriver CR. Age at onset and causes of disease. Perspect Biol Med 1986; 29: 437-60.
105. Addington AM, Gornick MC, Sporn AL etal. Polymorphisms in the 13q33.2 gene G72/G30 are associated with childhood-onset schizophrenia and psychosis not otherwise specified. Biol Psychiatry 2004; 55: 976-80.
106. Addington AM, Gornick MC, Shaw P etal. Neuregulin 1 (8p12) and childhood-onset schizophrenia: susceptibility haplotypes for diagnosis and brain developmental trajectories. Mol Psychiatry 2007; 12: 195-205.
107. Gornick MC, Addington AM, Sporn A etal. Dysbindin (DTNBP1, 6p22.3) is associated with childhood-onset psychosis and endophenotypes measured by the Premorbid Adjustment Scale (PAS). J Autism Dev Disord 2005; 35: 831-8.
108. Addington AM, Gornick M, Duckworth J etal. GAD1 (2q31.1), which encodes glutamic acid decarboxylase (GAD67), is associated with childhood-onset schizophrenia and cortical gray matter volume loss. Mol Psychiatry 2005; 10: 581-8.
109. Vyas NS, Kumra S, Puri BK. What insights can we gain from studying early onset schizophrenia? A neurodevelopmental pathway and beyond. Exp Rev Neurotherapeutics 2010; 11: 37-51.
110. Shprintzen RJ, Goldberg RB, Lewin ML etal. A new syndrome involving cleft palate, cardiac anomalies, typical facies, and learning disabilities: velo-cardio-facial syndrome. Cleft Palate J 1978; 15: 56-62.
111. Shprintzen RJ. Velo-cardio-facial syndrome: a distinctive behavioral phenotype. Ment Retard Dev Disabil Res Rev 2000; 6: 142-7.
112. Kelly D, Goldberg R, Wilson D etal. Confirmation that the velo-cardio-facial syndrome is associated with haploinsufficiency of genes at chromosome 22q11. Am J Med Genet 1993; 45: 308-12.
113. Pulver AE, Karayiorgou M, Lasseter VK etal. Follow-up of a report of a potential linkage for schizophrenia on chromosome 22q12-q13.1: part 2. Am J Med Genet 1994b; 54: 44-50.
114. Botto LD, May K, Fernhoff PM etal. A population-based study of the 22q11.2 deletion: phenotype, incidence, and contribution to major birth defects in the population. Pediatrics 2003; 112: 101-7.
115. Pulver AE, Nestadt G, Goldberg R etal. Psychotic illness in patients diagnosed with velo-cardio-facial syndrome and their relatives. J Nerv Ment Dis 1994a; 182: 476-8.
116. Papolos DF, Faedda GL, Veit S etal. Bipolar spectrum disorders in patients diagnosed with velo-cardio-facial syndrome: does a hemizygous deletion of chromosome 22q11 result in bipolar affective disorder? Am J Psychiatry 1996; 153: 1541-7.
117. Bassett AS, Chow EW. 22q11 deletion syndrome: a genetic subtype of schizophrenia. Biol Psychiatry 1999; 46: 882-91.
118. Murphy KC, Jones LA, Owen MJ. High rates of schizophrenia in adults with velo-cardiofacial syndrome. Arch Gen Psychiatry 1999; 56: 940-5.
119. Nicolson R, Giedd JN, Lenane M etal. Clinical and neurobiological correlates of cytogenetic abnormalities in childhood-onset schizophrenia. Am J Psychiatry 1999; 156: 1575-9.
120. Sporn A, Addington A, Reiss AL etal. 22q11 deletion syndrome in childhood onset schizophrenia: an update. Mol Psychiatry 2004; 9: 225-6.
121. Rapoport JL, Addington AM, Frangou S. The neurodevelopmental model of schizophrenia: update 2005. Mol Psychiatry 2005; 10: 434-49.
122. Ousley O, Rockers K, Dell ML etal. A review of neurocognitive and behavioral profiles associated with 22q11 deletion syndrome: implications for clinical evaluation and treatment. Curr Psychiatry Rep 2007; 9: 148-58.
123. Burgess CE, Lindblad K, Sidransky E etal. Large CAG/CTG repeats are associated with childhood onset schizophrenia. Mol Psychiatry 1998; 3: 321-7.
124. Eckstrand K, Addington AM, Stromberg T etal. Sex chromosome anomalies in chlidhood onset schizophrenia: an update. Mol Psychiatry 2008; 13: 910-11.
125. Sebat J, Lakshmi B, Troge J etal. Large-scale copy-number polymorphism in the human genome. Science 2004; 305: 525-28.
126. Pinto D, Marshall C, Feuk L, Scherer SW. Copy-number variation in control population cohorts. Hum Mol Genet 2007; 16: R168-73.
127. Wilson GM, Flibotte S, Chopra V, MeInyk BL, Honer WG, Holt RA. DNA copy-number analysis in bipolar disorder and schizophrenia reveals aberrations in genes involved in glutamate signaling. Hum Mol Genet 2006; 15: 743-9.
128. International Schizophrenia Consortium. Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature 2008; 455: 237-41.
129. Stefansson H, Rujescu D, Cichon S etal. Large recurrent microdeletions associasted with schizophrenia. Nature 2008; 455: 232-36.
130. Vrijenhoek T, Buizer-Voskamp JE, van der Stelt I etal. Recurrent CNVs disrupt three candidate genes in schizophrenia patients. Am J Human Genet 2008; 83: 504-10.
131. Xu B, Roos JL, Levy S, van Rensburg EJ, Gogos JA, Karayiorgou M. Strong association of de novo copy-number mutations with sporadic schizophrenia. Nat Genet 2008; 40: 880-5.
132. St Clair D. Copy-number variation and schizophrenia. Schizophr Bull 2009; 35: 9-12.
133. Walsh T, McClellan JM, McCarthy SE etal. Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science 2008; 320: 539-43.
134. Rujescu D, Ingason A, Cichon S etal. Disruption of the neurexin 1 gene is associated with schizophrenia. Hum Mol Genet 2008; 17: 458-65.
135. Andreasen N, Ehrhardt JC, Swazye VW 2nd etal. Magnetic resonance imaging of the brain in schizophrenia. The pathophysiologic significance of structural abnormalities. Arch Gen Psychiatry 1990; 47: 35-44.
136. Nopoulos P, Torres I, Flaum M, Andreasen NC, Ehrhardt JC, Yuh WT. Brain morphology in first-episode schizophrenia. Am J Psychiatry 1995; 152: 1721-3.
137. Gur RE, Turetsky BI, Cowell P etal. Temporolimbic volume reductions in schizophrenia. Arch Gen Psychiatry 2000; 57: 769-75.
138. Gur RE, Cowell P, Latshaw A etal. Reduced dorsal and orbital prefrontal gray matter volumes in schizophrenia. Schizophr Bull 2000; 9: 761-8.
139. Lawrie SM, Abukmeil SS. Brain abnormalities in schizophrenia: a systematic and quantitative review of volumetric magnetic resonance imaging studies. Br J Psychiatry 1998; 172: 110-20.
140. Jacobsen LK, Giedd JN, Rajapakse JC etal. Quantitative magnetic resonance imaging of the corpus callosum in childhood onset schizophrenia. Psychiatry Res 1997; 68: 77-86.
141. Puri BK. Progressive structural brain changes in schizophrenia. Exp Rev Neurother 2010; 10: 33-42.
142. Frazier JA, Giedd JN, Hamburger SD etal. Brain anatomic magnetic resonance imaging in childhood-onset schizophrenia. Arch Gen Psychiatry 1996; 53: 617-24.
143. Rapoport JL, Castellanos XF, Gogtay N, Janson K, Kohler S, Nelson P. Imaging normal and abnormal brain development: new perspectives for child psychiatry. Aust N Z J Psychiatry 2002; 35: 272-81.
144. Thompson PM, Vidal C, Giedd JN etal. Mapping adolescent brain change reveals dynamic wave of accelerated gray matter loss in very early-onset schizophrenia. Proc Natl Acad Sci USA 2001; 98: 11650-5.
145. Giedd JN, Jeffries NO, Blumenthal J etal. Childhood-onset schizophrenia: progressive brain changes during adolescence. Biol Psychiatry 1999; 46: 892-8.
146. Gogtay N, Sporn A, Clasen LS etal. Comparison of progressive cortical gray matter loss in childhood-onset schizophrenia with that in childhood-onset atypical psychoses. Arch Gen Psychiatry 2004; 61: 17-22.
147. Thomas MA, Ke Y, Levitt J etal. Preliminary study of frontal lobe 1H MR spectroscopy in childhood-onset schizophrenia. J Magn Reson Imaging 1998; 8: 841-6.
148. Kendi M, Kendi AT, Lehericy S etal. Structural and diffusion tensor imaging of the fornix in childhood- and adolescent-onset schizophrenia. J Am Acad Child Adolesc Psychiatry 2008; 47: 826-32.
149. Vyas NS, Patel NH, Nijran KS, Al-Nahhas A, Puri BK. Can PET/CT imaging advance our understanding of the neurobiology of schizophrenia? Nucl Med Commun 2010; 31: 91-3.
150. Patel NH, Vyas NS, Puri BK, Nijran KS, Al-Nahhas A. Positron emission tomography in schizophrenia: a new perspective. J Nucl Med 2010; 51: 11-20.
151. Vyas NS, Patel NH, Nijran KS, Al-Nahhas A, Puri BK. Insights into schizophrenia using positron emission tomography imaging: building the evidence and refining the focus. Br J Psychiatry 2010; 197: 3-4.