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Chapter 24 - Velocardiofacial syndrome (chromosome 22q11.2 deletion syndrome) as a model of schizophrenia

from Section 3 - Organic syndromes of schizophrenia

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1. Weinberger D. R. Implications of normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry, 1987. 44:660–9.
2. Andreasen N. C., Nopoulos P., O'Leary D. S., et al. Defining the phenotype of schizophrenia: cognitive dysmetria and its neural mechanisms. Biol Psychiatry, 1999. 46:908–20.
3. Hovatta I., Lichtermann D., Juvonen H., et al. Linkage analysis of putative schizophrenia gene candidate regions on chromosomes 3p, 5q, 6p, 8p, 20p and 22q in a population-based sampled Finnish family set. Mol Psychiatry, 1998. 3:452–7.
4. Shaw S. H., Kelly M., Smith A. B., et al. A genome-wide search for schizophrenia susceptibility genes. Am J Med Genet, 1998. 81:364–76.
5. Liu H., Abecasis G. R., Heath S. C., et al. Genetic variation in the 22q11 locus and susceptibility to schizophrenia. Proc Natl Acad Sci USA, 2002. 99:16859–64.
6. Kendler K. S. Hierarchy and heritability: the role of diagnosis and modeling in psychiatric genetics. Am J Psychiatry, 2002. 159:515–18.
7. Shprintzen R. J., Goldberg R., Golding-Kushner K. J., et al. Late-onset psychosis in the velo-cardio-facial syndrome. Am J Med Genet, 1992. 42:141–2.
8. Pulver A. E., Nestadt G., Goldberg R., et al. Psychotic illness in patients diagnosed with velo-cardio-facial syndrome and their relatives. J Nerv Ment Dis, 1994. 182:476–8.
9. Papolos D. F., Faedda G. L., Veit S., et al. 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.
10. Murphy K. C., Jones L. A., Owen M. J. High rates of schizophrenia in adults with velo-cardio-facial syndrome. Arch Gen Psychiatry, 1999. 56:940–5.
11. Chow E. W., Watson M., Young D. A., et al. Neurocognitive profile in 22q11 deletion syndrome and schizophrenia. Schizophr Res, 2006. 87:270–78.
12. Wilson D. I. Cross I. E., Wren C. Minimum prevalence of chromosome 22q11 deletions. Am J Hum Genet, 1994. 55:A169.
13. Tezenas Du M. S., Mendizabai H., Ayme S., et al. (1996) Prevalence of 22q11 microdeletion. J Med Genet, 1996. 33:719.
14. Shprintzen R. J. Velocardiofacial syndrome. Otolaryngol Clin North Am, 2000. 33:1217–40, vi.
15. Bassett A. S., Chow E. W. 22q11 deletion syndrome: a genetic subtype of schizophrenia. Biol Psychiatry, 1999. 46:882–91.
16. Bassett A. S., Hodgkinson K., Chow E. W., et al. 22q11 deletion syndrome in adults with schizophrenia. Am J Med Genet, 1998. 81:328–37.
17. Bassett A. S., Chow E. W., Husted J., et al. Clinical features of 78 adults with 22q11 Deletion Syndrome. Am J Med Genet A, 2005. 138:307–13.
18. Fraser W., Nolan M. (1994) Psychiatric disorders in mental retardation. In Mental Health in Mental Retardation, Bouras N. (Ed.). Cambridge: Cambridge University Press, pp. 79–92.
19. Karayiorgou M., Morris M. A., Morrow B., et al. Schizophrenia susceptibility associated with interstitial deletions of chromosome 22q11. Proc Natl Acad Sci USA, 1995. 92:7612–16.
20. Arinami T., Ohtsuki T., Takase K., et al. Screening for 22q11 deletions in a schizophrenia population. Schizophr Res, 2001. 52:167–70.
21. Sporn A., Addington A., Reiss A. L., et al. 22q11 deletion syndrome in childhood onset schizophrenia: an update. Mol Psychiatry, 2004. 9:225–6.
22. Andreasen N. C. A unitary model of schizophrenia: Bleuler's “fragmented phrene” as schizencephaly. Arch Gen Psychiatry, 1999. 56:781–7.
23. Rapoport J. L., Addington A. M., Frangou S., et al. The neurodevelopmental model of schizophrenia: update 2005. Mol Psychiatry, 2005. 10:434–49.
24. Keshavan M. S., Anderson S., Pettegrew J. W. Is schizophrenia due to excessive synaptic pruning in the prefrontal cortex? The Feinberg hypothesis revisited. J Psychiatr Res, 1994. 28:239–65.
25. Keshavan M. S. Development, disease and degeneration in schizophrenia: a unitary pathophysiological model. J Psychiatr Res, 1999. 33:513–21.
26. O'Callaghan E., Larkin C., Kinsella A., et al. Familial, obstetric, and other clinical correlates of minor physical anomalies in schizophrenia. Am J Psychiatry, 1991. 148:479–83.
26. Pantelis C., Yucel M., Wood S. J., et al. Early and late neurodevelopmental disturbances in schizophrenia and their functional consequences. Aust NZ J Psychiatry, 2003. 37:399–406.
27. Green M. F., Satz P., Gaier D. J., et al. Minor physical anomalies in schizophrenia. Schizophr Bull, 1989. 15:91–9.
28. Jones P., Rodgers B., Murray R., et al. Child development risk factors for adult schizophrenia in the British 1946 birth cohort. Lancet, 1994. 344:1398–1402.
29. Scutt L. E., Chow E. W., Weksberg R., et al. Patterns of dysmorphic features in schizophrenia. Am J Med Genet, 2001. 105:713–23.
30. Walker E. F., Savoie T., Davis D. Neuromotor precursors of schizophrenia. Schizophr Bull, 1994. 20:441–51.
31. Hollis C. Child and adolescent (juvenile onset) schizophrenia. A case control study of premorbid developmental impairments. Br J Psychiatry, 1995. 166:489–95.
32. Pantelis C., Maruff P. The cognitive neuropsychiatric approach to investigating the neurobiology of schizophrenia and other disorders. J Psychosom Res, 2002. 53:655–64.
33. Kessler R. C., Demler O., Frank R. G., et al. Prevalence and treatment of mental disorders, 1990 to 2003. N Engl J Med, 2005. 352:2515–23.
34. Cornblatt B. A., Erlenmeyer-Kimling L. Global attentional deviance as a marker of risk for schizophrenia: specificity and predictive validity. J Abnorm Psychol, 1985. 94:470–86.
35. Niemi L. T., Suvisaari J. M., Tuulio-Henriksson A., et al. Childhood developmental abnormalities in schizophrenia: evidence from high-risk studies. Schizophr Res, 2003. 60:239–58.
36. Morey R. A., Inan S., Mitchell T. V., et al. Imaging frontostriatal function in ultra-high-risk, early, and chronic schizophrenia during executive processing. Arch Gen Psychiatry, 2005. 62:254–62.
37. Kern R. S., Green M. F., Nuechterlein K. H., et al. NIMH-MATRICS survey on assessment of neurocognition in schizophrenia. Schizophr Res, 2004. 72:11–19.
38. Degreef G., Ashtari M., Bogerts B., et al. Volumes of ventricular system subdivisions measured from magnetic resonance images in first-episode schizophrenic patients. Arch Gen Psychiatry, 1992. 49:531–7.
39. Keshavan M. S., Rosenberg D., Sweeney J. A., et al. Decreased caudate volume in neuroleptic-naive psychotic patients. Am J Psychiatry, 1998. 155; 774–8.
40. Zipursky R. B., Lambe E. K., Kapur S., et al. Cerebral gray matter volume deficits in first episode psychosis. Arch Gen Psychiatry, 1998. 55:540–6.
41. DeQuardo J. R., Keshavan M. S., Bookstein F. L., et al. Landmark- based morphometric analysis of first-episode schizophrenia. Biol Psychiatry, 1999. 45:1321–8.
42. Shenton M. E., Dickey C. C., Frumin M., et al. A review of MRI findings in schizophrenia. Schizophr Res, 2001. 49:1–52.
43. Molina V., Sanchez J., Reig S., et al. N-acetyl-aspartate levels in the dorsolateral prefrontal cortex in the early years of schizophrenia are inversely related to disease duration. Schizophr Res, 2005. 73:209–19.
44. Nelson M. D., Saykin A. J., Flashman L. A., et al. Hippocampal volume reduction in schizophrenia as assessed by magnetic resonance imaging: a meta-analytic study. Arch Gen Psychiatry, 1998. 55:433–40.
45. Konick L. C., Friedman L. Meta-analysis of thalamic size in schizophrenia. Biol Psychiatry, 2001. 49:28–38.
46. Choi J. S., Kang D. H., Kim J. J., et al. Decreased caudal anterior cingulate gyrus volume and positive symptoms in schizophrenia. Psychiatry Res, 2005. 139:239–47.
47. Keshavan M. S., Diwadkar V. A., Montrose D. M., et al. Premorbid indicators and risk for schizophrenia: a selective review and update. Schizophr Res, 2005. 79:45–57.
48. Giedd J. N., Snell J. W., Lange N., et al. Quantitative magnetic resonance imaging of human brain development: ages 4–18. Cereb Cortex, 1996. 6:551–60.
49. Rapoport J. L., Castellanos F. X., Gogate N., et al. Imaging normal and abnormal brain development: new perspectives for child psychiatry. Aust N Z J Psychiatry, 2001. 35:272–81.
50. Zecevic N., Bourgeois J. P., Rakic P. Changes in synaptic density in motor cortex of rhesus monkey during fetal and postnatal life. Brain Res Dev Brain Res, 1989. 50:11–32.
51. Huttenlocher P. R., Dabholkar A. S. Regional differences in synaptogenesis in human cerebral cortex. J Comp Neurol, 1997. 387:167–78.
52. Giedd J. N., Clasen L. S., Lenroot R., et al. (2006) Puberty-related influences on brain development. Mol Cell Endocrinol, 2006. 254–5:154–62.
53. Sowell E. R., Thompson P. M., Leonard C. M., et al. Longitudinal mapping of cortical thickness and brain growth in normal children. J Neurosci, 2004. 24:8223–31.
54. Thompson P. M., Vidal C., Giedd J. N., et al. Mapping adolescent brain change reveals dynamic wave of accelerated grey matter loss in very early-onset schizophrenia. Proc Natl Acad Sci USA, 2001. 98:11650–5.
55. McGlashan T. H., Hoffman R. E. Schizophrenia as a disorder of developmentally reduced synaptic connectivity. Arch Gen Psychiatry, 2000. 57:637–48.
56. Gill M., Vallada H., Collier D., et al. A combined analysis of D22S278 marker alleles in affected sib-pairs: support for a susceptibility locus for schizophrenia at chromosome 22q12. Schizophrenia Collaborative Linkage Group (Chromosome 22). Am J Med Genet, 1996. 67:40–5.
57. Shprintzen R. J., Goldberg R. B., Young D., et al. The velo-cardio-facial syndrome: a clinical and genetic analysis. Pediatrics, 1981. 67:167–72.
58. Swillen A., Devriendt K., Legius E., et al. Intelligence and psychosocial adjustment in velocardiofacial syndrome: a study of 37 children and adolescents with VCFS. J Med Genet, 1997. 34:453–8.
59. Moss E. M., Batshaw M. L., Solot C. B., et al. Psychoeducational profile of the 22q11.2 microdeletion: a complex pattern. J Pediatr, 1999. 134:193–8.
60. Woodin M., Wang P. P., Aleman D., et al. Neuropsychological profile of children and adolescents with the 22q11.2 microdeletion. Genet Med, 2001. 3:34–9.
61. Glaser B., Mumme D. L., Blasey C., et al. Language skills in children with velocardiofacial syndrome (deletion 22q11.2). J Pediatr, 2002. 140:753–8.
62. Gerdes M., Solot C., Wang P. P., et al. Cognitive and behavior profile of preschool children with chromosome 22q11.2 deletion. Am J Med Genet, 1999 85:127–33.
63. Sobin C., Kiley-Brabeck K., Daniels S., et al. Neuropsychological characteristics of children with the 22q11 Deletion Syndrome: a descriptive analysis. Child Neuropsychol, 2005a. 11:39–53.
64. Rovet J. F., Buchanan L. (1999) Turner syndrome: a cognitive neuroscience approach. In Neurodevelopmental Disorders, Tager F. (Ed.). Cambridge, Mass.: The MIT Press, pp. 223–50.
65. Sobin C., Kiley-Brabeck K., Karayiorgou M. Associations between prepulse inhibition and executive visual attention in children with the 22q11 deletion syndrome. Mol Psychiatry, 2005b. 10:553–62.
66. Baker K., Baldeweg T., Sivagnanasundaram S., et al. COMT Val108/158 Met modifies mismatch negativity and cognitive function in 22q11 deletion syndrome. Biol Psychiatry, 2005. 58:23–31.
67. Bish J. P., Ferrante S. M., Donald-McGinn D., et al. Maladaptive conflict monitoring as evidence for executive dysfunction in children with chromosome 22q11.2 deletion syndrome. Dev Sci, 2005. 8:36–43.
68. Simon T. J., Bearden C. E., Mc-Ginn D. M., et al. Visuospatial and numerical cognitive deficits in children with chromosome 22q11.2 deletion syndrome. Cortex, 2005a. 41:145–55.
69. Lewandowski K. E., Shashi V., Berry P. M., et al. Schizophrenic-like neurocognitive deficits in children and adolescents with 22q11 deletion syndrome. Am J Med Genet, B Neuropsychiatr Genet, 2007. 144:27–36.
70. Buchanan R. W., Francis A., Arango C., et al. Morphometric assessment of the heteromodal association cortex in schizophrenia. Am J Psychiatry, 2004. 161:322–31.
71. Swillen A., Devriendt K., Legius E., et al. The behavioural phenotype in velo-cardio-facial syndrome (VCFS): from infancy to adolescence. Genet Couns, 1999. 10:79–88.
72. Swillen A., Vogels A., Devriendt K., et al. Chromosome 22q11 deletion syndrome: update and review of the clinical features, cognitive-behavioral spectrum, and psychiatric complications. Am J Med Genet, 2000. 97:128–35.
73. Arnold P. D., Siegel-Bartelt J., Cytrynbaum C., et al. Velo-cardio-facial syndrome: implications of microdeletion 22q11 for schizophrenia and mood disorders. Am J Med Genet, 2001. 105:354–62.
74. Gothelf D., Presburger G., Zohar A. H., et al. Obsessive-compulsive disorder in patients with velocardiofacial (22q11 deletion) syndrome. Am J Med Genet, B Neuropsychiatr Genet, 2004. 126:99–105.
75. Heineman-de Boer J. A., Van Haelst M. J., Cordia-de H. M., et al. Behavior problems and personality aspects of 40 children with velo-cardio-facial syndrome. Genet Couns, 1999. 10:89–93.
76. Feinstein C., Eliez S., Blasey C., et al. Psychiatric disorders and behavioral problems in children with velocardiofacial syndrome: usefulness as phenotypic indicators of schizophrenia risk. Biol Psychiatry, 2002. 51:312–18.
77. Murphy K. C., Owen M. J. Velo-cardio-facial syndrome: a model for understanding the genetics and pathogenesis of schizophrenia. Br J Psychiatry, 2001. 179:397–402.
78. Murphy K. C. Annotation: velo-cardio-facial syndrome. J Child Psychol Psychiatry, 2005. 46:563–71.
79. Debbane M., Glaser B., David M. K., et al. (2006a) Psychotic symptoms in children and adolescents with 22q11.2 deletion syndrome: Neuropsychological and behavioral implications. Schizophr Res, 2006a. 84:187–93.
80. Baker K. D., Skuse D. H. Adolescents and young adults with 22q11 deletion syndrome: psychopathology in an at-risk group. Br J Psychiatry, 2005. 186:115–20.
81. Cannon M., Caspi A., Moffitt T. E., et al. Evidence for early-childhood, pan-developmental impairment specific to schizophreniform disorder: results from a longitudinal birth cohort. Arch Gen Psychiatry, 2002. 59:449–56.
82. Davalos D. B., Compagnon N., Heinlein S., et al. Neuropsychological deficits in children associated with increased familial risk for schizophrenia. Schizophr Res, 2004. 67:123–30.
83. Mitnick R. J., Bello J. A., Shprintzen R. J. Brain anomalies in velo-cardio-facial syndrome. Am J Med Genet, 1994. 54:100–6.
84. Bingham P. M., Zimmerman R. A., Donald-McGinn D., et al. Enlarged Sylvian fissures in infants with interstitial deletion of chromosome 22q11. Am J Med Genet, 1997. 74:538–43.
85. Vataja R., Elomaa E. Midline brain anomalies and schizophrenia in people with CATCH 22 syndrome. Br J Psychiatry, 1998. 172:518–20.
86. Chow E. W., Mikulis D. J., Zipursky R. B., et al. Qualitative MRI findings in adults with 22q11 deletion syndrome and schizophrenia. Biol Psychiatry, 1999. 46:1436–42.
87. Shashi V., Muddasani S., Santos C. C., et al. Abnormalities of the corpus callosum in nonpsychotic children with chromosome 22q11 deletion syndrome. Neuroimage, 2004. 21:1399–406.
88. Van A. T., Daly E., Robertson D., et al. Structural brain abnormalities associated with deletion at chromosome 22q11: quantitative neuroimaging study of adults with velo-cardio-facial syndrome. Br J Psychiatry, 2001. 178:412–19.
89. Usiskin S. I., Nicolson R., Krasnewich D. M., et al. Velocardiofacial syndrome in childhood-onset schizophrenia. J Am Acad Child Adolesc Psychiatry, 1999. 38:1536–43.
90. Eliez S., Schmitt J. E., White C. D., et al. Children and adolescents with velocardiofacial syndrome: a volumetric MRI study. Am J Psychiatry, 2000. 157:409–15.
91. Katesa W. R., Burnettea C. P. Posterior cortical white matter anomalies in velocardiofacial syndrome. pp 1S-173S Biol Psychiatry, 2000. 47(Suppl 1): S102–73S.
92. Eliez S., Blasey C. M., Schmitt E. J., et al. Velocardiofacial syndrome: are structural changes in the temporal and mesial temporal regions related to schizophrenia? Am J Psychiatry, 2001. 158:447–53.
93. Simon T. J., Ding L., Bish J. P., et al. Volumetric, connective, and morphologic changes in the brains of children with chromosome 22q11.2 deletion syndrome: an integrative study. Neuroimage, 2005b. 25:169–80.
94. Bearden C. E., van Erp T. G., Dutton R. A., et al. Mapping cortical thickness in children with 22q11.2 deletions. Cereb Cortex, 2007. 17:1889–98. [Epub Oct 20, 2006.]
95. Debbane M., Schaer M., Farhoumand R., et al. Hippocampal volume reduction in 22q11.2 deletion syndrome. Neuropsychologia, 2006b. 44:2360–5.
96. Sugama S., Bingham P. M., Wang P. P., et al. Morphometry of the head of the caudate nucleus in patients with velocardiofacial syndrome (del 22q11.2). Acta Paediatr, 2000. 89:546–9.
97. Eliez S., Barnea-Goraly N., Schmitt J. E., et al. Increased basal ganglia volumes in velo-cardio-facial syndrome (deletion 22q11.2). Biol Psychiatry, 2002. 52:68–70.
98. Kates W. R., Burnette C. P., Bessette B. A., et al. Frontal and caudate alterations in velocardiofacial syndrome (deletion at chromosome 22q11.2). J Child Neurol, 2004. 19:337–42.
99. Campbell L. E., Daly E., Toal F., et al. Brain and behaviour in children with 22q11.2 deletion syndrome: a volumetric and voxel-based morphometry MRI study. Brain, 2006. 129:1218–28.
100. Kates W. R., Miller A. M., AbdulSabur N., et al. Temporal lobe anatomy and psychiatric symptoms in velocardiofacial syndrome (22q11.2 deletion syndrome). J Am Acad Child Adolesc Psychiatry, 2006. 45:587–95.
101. Antshel K. M., Conchelos J., Lanzetta G., et al. Behavior and corpus callosum morphology relationships in velocardiofacial syndrome (22q11.2 deletion syndrome). Psychiatry Res, 2005. 138:235–45.
102. Keshavan M. S., Dick E., Mankowski I., et al. Decreased left amygdala and hippocampal volumes in young offspring at risk for schizophrenia Schizophr Res, 2002a. 58:173–83.
103. Keshavan M. S., Diwadkar V. A., Harenski K., et al. Abnormalities of the corpus callosum in first episode, treatment naive schizophrenia. J Neurol Neurosurg Psychiatry, 2002b. 72:757–60.
104. Bearden C. E., van Erp T. G., Monterosso J. R., et al. Regional brain abnormalities in 22q11.2 deletion syndrome: association with cognitive abilities and behavioral symptoms. Neurocase, 2004b. 10:198–206.
105. Feinberg I. Schizophrenia: caused by a fault in programmed synaptic elimination during adolescence? J Psychiatr Res, 1982. 17:319–34.
106. Gothelf D., Frisch A., Munitz H., et al. Clinical characteristics of schizophrenia associated with velo-cardio-facial syndrome. Schizophr Res, 1999. 35:105–12.
107. Bassett A. S., Chow E. W., AbdelMalik P., et al. The schizophrenia phenotype in 22q11 deletion syndrome. Am J Psychiatry, 2003. 160:1580–6.
108. Meehl P. E. Toward an integrated theory of schizotaxia, schizotypy and schizophrenia. J Personality Disorders, 1990. 4:1–99.
109. Van A. T., Henry J., Morris R., et al. Cognitive deficits associated with schizophrenia in velo-cardio-facial syndrome. Schizophr Res, 2004b. 70:223–32.
110. Barnea-Goraly N., Menon V., Krasnow B., et al. Investigation of white matter structure in velocardiofacial syndrome: a diffusion tensor imaging study. Am J Psychiatry, 2003. 160:1863–9.
111. Chow E. W., Zipursky R. B., Mikulis D. J., et al. Structural brain abnormalities in patients with schizophrenia and 22q11 deletion syndrome. Biol Psychiatry, 2002. 51:208–15.
112. Van A. T., Daly E., Henry J., et al. Brain anatomy in adults with velocardiofacial syndrome with and without schizophrenia: preliminary results of a structural magnetic resonance imaging study. Arch Gen Psychiatry, 2004a. 61:1085–96.
113. Gothelf D., Gruber R., Presburger G., et al. Methylphenidate treatment for attention-deficit/hyperactivity disorder in children and adolescents with velocardiofacial syndrome: an open-label study. J Clin Psychiatry, 2003. 64:1163–9.
114. Lasseter V. K., Pulver A. E., Wolyniec P. S., et al. (1995) Follow-up report of potential linkage for schizophrenia on chromosome 22q: Part 3. Am J Med Genet, 1995. 60:172–3.
115. Lachman H. M., Kelsoe J. R., Remick R. A., et al. Linkage studies suggest a possible locus for bipolar disorder near the velo-cardio-facial syndrome region on chromosome 22. Am J Med Genet, 1997. 74:121–8.
116. Kelsoe J. R., Spence M. A., Loetscher E., et al. A genome survey indicates a possible susceptibility locus for bipolar disorder on chromosome 22. Proc Natl Acad Sci USA, 2001. 98:585–90.
117. Funke B., Saint-Jore B., Puech A., et al. Characterization and mutation analysis of goosecoid-like (GSCL), a homeodomain-containing gene that maps to the critical region for VCFS/DGS on 22q11. Genomics, 1997. 46:364–72.
118. Sirotkin H., O'Donnell H., DasGupta R., et al. (1997) Identification of a new human catenin gene family member (ARVCF) from the region deleted in velo-cardio-facial syndrome. Genomics, 1997. 41:75–83.
119. Kurahashi H., Nakayama T., Osugi Y., et al. Deletion mapping of 22q11 in CATCH22 syndrome: identification of a second critical region. Am J Hum Genet, 1996. 58:1377–81.
120. Kurahashi H., Tsuda E., Kohama R., et al. Another critical region for deletion of 22q11: a study of 100 patients. Am J Med Genet, 1997. 72:180–5.
121. Karayiorgou M., Gogos J. A. The molecular genetics of the 22q11-associated schizophrenia. Brain Res Mol Brain Res, 2004. 132:95–104.
122. Carey J. C., Viskochil D. H. Neurofibromatosis type 1: a model condition for the study of the molecular basis of variable expressivity in human disorders. Am J Med Genet, 1999. 89:7–13.
123. Breuning M. H. Phenotypic variability: genetics and chance–deletion 22q11 and schizophrenia. Ned Tijdschr Geneeskd, 2002. 146:2016–19.
124. Li T., Ma X., Sham P. C., et al. Evidence for association between novel polymorphisms in the PRODH gene and schizophrenia in a Chinese population. Am J Med Genet, B Neuropsychiatr Genet, 2004. 129:13–15.
125. Mukai J., Liu H., Burt R. A., et al. Evidence that the gene encoding ZDHHC8 contributes to the risk of schizophrenia. Nat Genet, 2004. 36:725–31.
126. Bender H. U., Almashanu S., Steel G., et al. Functional consequences of PRODH missense mutations. Am J Hum Genet, 2005. 76:409–20.
127. Karoum F., Chrapusta S. J., Egan M. F. 3-Methoxytyramine is the major metabolite of released dopamine in the rat frontal cortex: reassessment of the effects of antipsychotics on the dynamics of dopamine release and metabolism in the frontal cortex, nucleus accumbens, and striatum by a simple two pool model. J Neurochem, 1994. 63:972–9.
128. Weinberger D. R., Egan M. F., Bertolino A., et al. Prefrontal neurons and the genetics of schizophrenia. Biol Psychiatry, 2001. 50:825–44.
129. Aksoy S., Klener J., Weinshilboum R. M. Catechol O-methyltransferase pharmacogenetics: photoaffinity labelling and western blot analysis of human liver samples. Pharmacogenetics, 1993. 3:116–22.
130. Gogos J. A., Morgan M., Luine V., et al. Catechol-O-methyl-transferase-deficient mice exhibit sexually dimorphic changes in catecholamine levels and behavior. Proc Natl Acad Sci USA, 1998. 95:9991–6.
131. Egan M. F., Goldberg T. E., Kolachana B. S., et al. Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc Natl Acad Sci USA, 2001. 98:6917–22.
132. Bilder R. M., Volavka J., Czobor P., et al. Neurocognitive correlates of the COMT Val(158)Met polymorphism in chronic schizophrenia. Biol Psychiatry, 2002. 52:701–7.
133. Malhotra A. K., Kestler L. J., Mazzanti C., et al. A functional polymorphism in the COMT gene and performance on a test of prefrontal cognition. Am J Psychiatry, 2002. 159:652–4.
134. Li T., Sham P. C., Vallada H., et al. Preferential transmission of the high activity allele of COMT in schizophrenia. Psychiatr Genet, 1996. 6:131–3.
135. Avramopoulos D., Stefanis N. C., Hantoumi I., et al. Higher scores of self reported schizotypy in healthy young males carrying the COMT high activity allele. Mol Psychiatry, 2002. 7:706–11.
136. Wonodi I., Stine O. C., Mitchell B. D., et al. Association between Val108/158 Met polymorphism of the COMT gene and schizophrenia. Am J Med Genet B Neuropsychiatr Genet, 2003. 120:47–50.
137. Munafo M. R., Bowes L., Clark T. G., et al. (2005) Lack of association of the COMT (Val158/108 Met) gene and schizophrenia: a meta-analysis of case-control studies. Mol Psychiatry, 2005. 10:765–70.
138. Bearden C. E., Jawad A. F., Lynch D. R., et al. Effects of a functional COMT polymorphism on prefrontal cognitive function in patients with 22q11.2 deletion syndrome. Am J Psychiatry, 2004a. 161:1700–2.
139. Shashi V., Keshavan M. S., Howard T. D., et al. Cognitive correlates of a functional COMT polymorphism in children with 22q11.2 deletion syndrome. Clin Genet, 2006. 69:234–8.
140. Gothelf D., Michaelovsky E., Frisch A., et al. Association of the low-activity COMT 158Met allele with ADHD and OCD in subjects with velocardiofacial syndrome. Int J Neuropsychopharmacol, 2007. 10:301–8. [Epub May 31, 2006.]
141. Gothelf D., Eliez S., Thompson T., et al. COMT genotype predicts longitudinal cognitive decline and psychosis in 22q11. 2 deletion syndrome. Nat Neurosci, 2005. 8:1500–2.
142. Bassett A. S., Caluseriu O., Weksberg R., et al. Catechol-O-methyl transferase and expression of schizophrenia in 73 adults with 22q11 deletion syndrome. Biol Psychiatry, 2007. 61:1135–40. [Epub Jan 9, 2007.]
143. Goldman-Rakic P. S., Muly E. C. III, Williams G. V. D(1) receptors in prefrontal cells and circuits. Brain Res Brain Res Rev, 2000. 31:295–301.
144. Davis K. L., Kahn R. S., Ko G., et al. Dopamine in schizophrenia: a review and reconceptualization. Am J Psychiatry, 1991. 148:1474–86.
145. Goldman-Rakic, P. S. (1991) Prefrontal cortical dysfunction in schizophrenia: the relevance of working memory. In Psychopathology and the Brain, Carroll B. J. and Barrett J. E. (Eds.). New York: Raven Press, pp. 1–23.
146. Braver T. S., Barch D. M., Cohen J. D. Cognition and control in schizophrenia: a computational model of dopamine and prefrontal function. Biol Psychiatry, 1999. 46:312–28.
147. Chen X., Wang X., O'Neill A. F., et al. Variants in the catechol-o-methyltransferase (COMT) gene are associated with schizophrenia in Irish high-density families. Mol Psychiatry, 2004b. 9:962–7.
148. Palmatier M. A., Pakstis A. J., Speed W., et al. COMT haplotypes suggest P2 promoter region relevance for schizophrenia. Mol Psychiatry, 2004. 9:859–70.
149. Handoko H. Y., Nyholt D. R., Hayward N. K., et al. Separate and interacting effects within the catechol-O-methyltransferase (COMT) are associated with schizophrenia. Mol Psychiatry, 2005. 10:589–97.
150. Fremeau R. T. Jr., Caron M. G., Blakely R. D. Molecular cloning and expression of a high affinity L-proline transporter expressed in putative glutamatergic pathways of rat brain. Neuron, 1992. 8:915–26.
151. Renick S. E., Kleven D. T., Chan J., et al. The mammalian brain high-affinity L-proline transporter is enriched preferentially in synaptic vesicles in a subpopulation of excitatory nerve terminals in rat forebrain. J Neurosci, 1999. 19:21–33.
152. Goff D. C., Coyle J. T. The emerging role of glutamate in the pathophysiology and treatment of schizophrenia. Am J Psychiatry, 2001. 158:1367–77.
153. Hahn C. G., Wang H. Y., Cho D. S., et al. Altered neuregulin 1-erbB4 signaling contributes to NMDA receptor hypofunction in schizophrenia. Nat Med, 2006. 12:824–8.
154. Paterlini M., Zakharenko S. S., Lai W. S., et al. Transcriptional and behavioral interaction between 22q11. 2 orthologs modulates schizophrenia-related phenotypes in mice. Nat Neurosci, 2005. 8:1586–94.
155. Maxwell S. A., Davis G. E. Differential gene expression in p53-mediated apoptosis-resistant vs. apoptosis-sensitive tumor cell lines. Proc Natl Acad Sci USA, 2000. 97:13009–14.
156. Williams H. J., Williams N., Spurlock G., et al. Detailed analysis of PRODH and PsPRODH reveals no association with schizophrenia. Am J Med Genet B Neuropsychiatr Genet, 2003b. 120:42–6.
157. Jacquet H., Rapoport J. L., Hecketsweiler B., et al. (2006) Hyperprolinemia is not associated with childhood onset schizophrenia. Am J Med Genet B Neuropsychiatr Genet, 2006. 141:192.
158. Williams H. J., Williams N., Spurlock G., et al. Association between PRODH and schizophrenia is not confirmed. Mol Psychiatry, 2003a. 8:644–5.
159. Raux G., Bumsel E., Hecketsweiler B., et al. (2006) Involvement of hyperprolinemia in cognitive and psychiatric features of the 22q11 deletion syndrome. Hum Mol Genet, 2007. 16:83–91. [Epub Nov 29, 2006.]
160. El-Husseini A. E., Craven S. E., Chetkovich D. M., et al. Dual palmitoylation of PSD-95 mediates its vesiculotubular sorting, postsynaptic targeting, and ion channel clustering. J Cell Biol, 2000. 148:159–72.
161. Chen W. Y., Shi Y. Y., Zheng Y. L., et al. Case-control study and transmission disequilibrium test provide consistent evidence for association between schizophrenia and genetic variation in the 22q11 gene ZDHHC8. Hum Mol Genet, 2004a. 13:2991–5.
162. De L. A., Pasini A., Amati F., et al. Association study of a promoter polymorphism of UFD1L gene with schizophrenia. Am J Med Genet, 2001. 105:529–33.
163. Srivastava D., Yamagishi H. Reply: role of the dHAND-UFD1L pathway. Trends Genet, 1999. 15:253–4.
164. Yagi H., Furutani Y., Hamada H., et al. Role of TBX1 in human del22q11.2 syndrome. Lancet, 2003. 362:1366–73.
165. Paylor R., Glaser B., Mupo A., et al. Tbx1 haploinsufficiency is linked to behavioral disorders in mice and humans: implications for 22q11 deletion syndrome. Proc Natl Acad Sci USA, 2006. 103:7729–34.
166. Maynard T. M., Haskell G. T., Peters A. Z., et al. (2003) A comprehensive analysis of 22q11 gene expression in the developing and adult brain. Proc Natl Acad Sci USA, 2003. 100:14433–8.
167. Braff D. L., Geyer M. A., Swerdlow N. R. Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies. Psychopharmacology (Berl), 2001. 156:234–58.
168. Lindsay E. A., Botta A., Jurecic V., et al. Congenital heart disease in mice deficient for the DiGeorge syndrome region. Nature, 1999. 401:379–83.
169. Long J. M., Laporte P., Merscher S., et al. Behavior of mice with mutations in the conserved region deleted in velocardiofacial/DiGeorge syndrome. Neurogenetics, 2006. 7:247–57.
170. Paylor R., McIlwain K. L., McAninch R., et al. Mice deleted for the DiGeorge/velocardiofacial syndrome region show abnormal sensorimotor gating and learning and memory impairments. Hum Mol Genet, 2001. 10:2645–50.
171. Gogos J. A., Santha M., Takacs Z., et al. The gene encoding proline dehydrogenase modulates sensorimotor gating in mice. Nat Genet, 1999. 21:434–9.
172. Hiroi N., Zhu H., Lee M., et al. A 200-kb region of human chromosome 22q11.2 confers antipsychotic-responsive behavioral abnormalities in mice. Proc Natl Acad Sci USA, 2005. 102:19132–7.
173. Jurata L. W., Gallagher P., Lemire A. L., et al. Altered expression of hippocampal dentate granule neuron genes in a mouse model of human 22q11 deletion syndrome. Schizophr Res, 2006. 88:251–9.
174. Altar C. A., Jurata L. W., Charles V., et al. Deficient hippocampal Neuron, expression of proteasome, ubiquitin, and mitochondrial genes in multiple schizophrenia cohorts. Biol Psychiatry, 2005. 58:85–96.