The Singapore flagship programme in translational and clinical research in psychosis

Early Intervention in Psychiatry

Volumn 5, Issue 4, 2011, Pages 290-300

  Chong, Siow Ann ^a   Campbell, Alastair ^b   Chee, Michael ^c   Liu, Jianjun ^d   Marx, Christine ^e   Mcgorry, Patrick ^f   Subramaniam, Mythily ^a   Yung, Alison ^f   Keefe, Richard S E ^e  

^a INSTITUTE OF MENTAL HEALTH   (Singapore)

^b NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^c NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^d GENOME INSTITUTE OF SINGAPORE   (Singapore)

^e DUKE UNIVERSITY MEDICAL CENTER   (United States)

^f UNIVERSITY OF MELBOURNE   (Australia)

Author keywords

Genetics; Neurocognition; Pregnenolone; Schizophrenia; Ultra high risk

Indexed keywords

3ALPHA HYDROXY 5ALPHA PREGNAN 20 ONE; ACETYLCHOLINE; D AP5; DIZOCILPINE; N METHYL DEXTRO ASPARTIC ACID; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; PREGNENOLONE; PREGNENOLONE DERIVATIVE; PREGNENOLONE SULFATE; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; ANTERIOR CINGULATE; AUTISM; BIPOLAR DISORDER; CLINICAL RESEARCH; COGNITION; COGNITIVE DEFECT; COPY NUMBER VARIATION; DISEASE COURSE; DISEASE PREDISPOSITION; DRUG BLOOD LEVEL; DRUG DOSE TITRATION; FUNCTIONAL MAGNETIC RESONANCE IMAGING; GENE EXPRESSION; GENE EXPRESSION PROFILING; GENETIC ANALYSIS; GENETIC ASSOCIATION; GENETIC HETEROGENEITY; GENETIC RISK; GENOME ANALYSIS; HEALTH PROGRAM; HUMAN; LEARNING; LIPIDOMICS; MEMORY; NEUROIMAGING; NEUROPSYCHOLOGY; PARKINSON DISEASE; PHENOTYPE; POLITICS; PREDICTION; PREDICTIVE VALIDITY; PREFRONTAL CORTEX; PRIORITY JOURNAL; PSYCHOSIS; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SCHIZOPHRENIA; SCORING SYSTEM; SINGAPORE; SINGLE DRUG DOSE; SINGLE NUCLEOTIDE POLYMORPHISM; SURFACE ENHANCED LASER DESORPTION IONIZATION TIME OF FLIGHT MASS SPECTROMETRY; TRANSLATIONAL RESEARCH;

BIOLOGICAL MARKERS; GENOME-WIDE ASSOCIATION STUDY; HUMANS; METABOLOMICS; NEUROIMAGING; NEUROPSYCHOLOGY; PHENOTYPE; PSYCHOTIC DISORDERS; RISK FACTORS; SCHIZOPHRENIA; SINGAPORE; TRANSLATIONAL MEDICAL RESEARCH;

EID: 80055047560     PISSN: 17517885     EISSN: 17517893     Source Type: Journal    
DOI: 10.1111/j.1751-7893.2011.00304.x     Document Type: Review

References (108)

1. Sullivan PF, Kendler KS, Neal MC. Schizophrenia as a complex trait. Arch Gen Psychiatry 2003; 60: 1187-92.
2. McGuffin P, Riley B, Plomin R. Genomics and behavior: toward behavioral genomics. Science 2001; 291: 1232-49.
3. Buckley PG, Mantripragada KK, Piotrowski A, Diaz de Ståhl T, Dumanski JP. Copy-number polymorphisms: mining the tip of an iceberg. Trends Genet 2005; 21: 315-7.
4. Sebat J. Major changes in our DNA lead to major changes in our thinking. Nat Genet 2007; 39 (Suppl.): S3-S5.
5. Feuk L, Carson AR, Scherer SW. Structural variation in the human genome. Nat Rev Genet 2006; 7: 85-97.
6. Cohen J. GENOMICS: DNA duplications and deletions help determine health. Science 2007; 317: 1315-17.
7. Keefe RS, Goldberg TE, Harvey PD, Gold JM, Poe MP, Coughenour L. The brief assessment of cognition in schizophrenia: reliability, sensitivity, and comparison with a standard neurocognitive battery. Schizophr Res 2004; 68: 283-97.
8. Benton AL, Hamsher K, Varney NR, Spreen O. Contributions to Neuropsychological Assessment. New York: Oxford University Press, 1983.
9. Wechsler D. Wechsler Adult Intelligence Scale-III. San Antonio, TX: The Psychological Corporation, 1997.
10. Cornblatt BA, Risch NJ, Faris G, Friedman D, Erlenmeyer-Kimling L. The Continuous Performance Test, identical pairs version (CPT-IP), I: new findings about sustained attention in normal families. Psychiatry Res 1988; 26: 223-38.
11. Axelrod BN, Henry RR, Woodward JL. Analysis of a abbreviated form of the Wisconsin Card Sorting Test. Clin Neuropsychol 1992; 6: 27-31.
12. Annet M. A Single Gene Explanation of Right and Left Handedness and Brainedness. Coventry, UK: Lanchester Polytechnic, 1978.
13. Yung AR, McGorry PD. The prodromal phase of first episode psychosis: past and current conceptualizations. Schizophr Bull 1996; 22: 353-70.
14. McGorry PD, Singh B. Schizophrenia: risk and possibility. In: Burrows G, ed. Handbook of Studies on Preventive Psychiatry. Amsterdam: Elsevier, 1995; 491-514.
15. Yung AR, McGorry PD, McFarlane CA, Jackson HJ, Patton GC, Rakkar A. Monitoring and care of young people at incipient risk of psychosis. Schizophr Bull 1996; 22: 283-303.
16. Yung AR, Yuen HP, McGorry PD etal. Mapping the onset of psychosis - the Comprehensive Assessment of at Risk Mental States (CAARMS). Aust N Z J Psychiatry 2005; 39: 964-71.
17. Miller TJ, McGlashan TH, Woods SW etal. Symptom assessment in schizophrenic prodromal states. Psychiatr Q 1999; 70: 273-87.
18. Skeate A, Patterson P, BirchWood M. Transition to psychosis in a high-risk sample: the experience of ED: IT, Birmingham UK. Schizophr Res 2004; 70 (Suppl. 1): s44.
19. Miller TJ, McGlashan TH, Rosen JL etal. Prospective diagnosis of the initial prodrome for schizophrenia based on the Structured Interview for Prodromal Syndromes: preliminary evidence of interrater reliability and predictive validity. Am J Psychiatry 2002; 159: 863-5.
20. Yung AR, Nelson B, Stanford C etal. Validation of 'prodromal' criteria to detect individuals at ultra high risk of psychosis: 2year follow-up. Schizophr Res 2008; 105: 10-7.
21. Cannon TD, Cadenhead K, Cornblatt B etal. Prediction of psychosis in youth at high clinical risk: a multisite longitudinal study in North America. Arch Gen Psychiatry 2008; 65: 28-37.
22. Haroun N, Dunn L, Haroun A, Cadenhead KS. Risk and protection in prodromal schizophrenia: ethical implications for clinical practice and future research. Schizophr Bull 2006; 32: 166-78.
23. Yung AR, Buckby JA, Cosgrave EM etal. Association between psychotic experiences and depression in a clinical sample over 6months. Schizophr Res 2007; 91: 246-53.
24. Corcoran C, Malaspina D, Hercher L. Prodromal interventions for schizophrenia vulnerability: the risks of being 'at risk'. Schizophr Res 2005; 73: 173-84.
25. Comblatt BA, Lencz T, Kane JM. Treatment of the schizophrenia prodrome: is it presently ethical? Schizophr Res 2001; 51: 31-8.
26. McClellan JM, Susser E, King MC. Schizophrenia: a common disease caused by multiple rare alleles. Br J Psychiatry 2007; 190: 194-99.
27. McGlashan TH. Psychosis treatment prior to psychosis onset: ethical issues. Schizophr Res 2001; 51: 47-54.
28. McGorry PD, Yung A, Phillips L. Ethics and early intervention in psychosis: keeping up the pace and staying in step. Schizophr Res 2001; 51: 17-29.
29. Addington J, Cadenhead KS, Cannon TD etal. North American prodrome longitudinal study: a collaborative multisite approach to prodromal schizophrenia research. Schizophr Bull 2007; 33: 665-72.
30. Bell RQ. Multiple-risk cohorts and segmenting risk as solutions to the problem of false positives in risk for the major psychoses. Psychiatry 1992; 55: 370-81.
31. Hafner H, Maurer K, Loffler W etal. The epidemiology of early schizophrenia. Influence of age and gender on onset and early course. Br J Psychiatry 1994; 164 (Suppl. 23): 29-38.
32. Chong SA, Wong J, Verma S etal. The mental health screening of conscripts for the Singapore Armed Forces: rationale, objectives and design. Mil Med 2007; 172: 1245-9.
33. Brewer WJ, Wood SJ, Phillips LJ etal. Generalized and specific cognitive performance in clinical high-risk cohorts: a review highlighting potential vulnerability markers for psychosis. Schizophr Bull 2006; 32: 538-55.
34. Correll CU, Hauser M, Auther AM, Cornblatt BA. Research in people with psychosis risk syndrome: a review of the current evidence and future directions. J Child Psychol Psychiatry 2010; 51: 390-431.
35. Gregory RL. Perceptions as hypotheses. Philos Trans R Soc Lond B Biol Sci 1980; 290: 181-97.
36. Edelman GM. The Remembered Present A Biological Theory of Consciousness. New York: Basic Books, 1989.
37. Snyder AW. Breaking mindset. Mind Lang 1998; 13: 1-10.
38. Hawkins J, Blakeslee S. On Intelligence. New York: Times Books, 2004.
39. Gregory RL. Perceptual illusions and brain models. Proc R Soc Lond B Biol Sci 1968; 171: 279-96.
40. Gregory RL. Perceptions of knowledge. Nature 2001; 410: 21-21.
41. Kraus MS, Keefe RSE, Krishnan RK. Memory-prediction errors and their consequences in schizophrenia. Neuropsychol Rev 2009; 19: 336-352. [epub ahead of print].
42. Marvel CL, Schwartz BL, Howard DV, Howard JH Jr. Implicit learning of non-spatial sequences in schizophrenia. J Int Neuropsychol Soc 2005; 11: 659-67.
43. Brune M, Bodenstein L. Proverb comprehension reconsidered 'theory of mind' and the pragmatic use of language in schizophrenia. Schizophr Res 2005; 75: 233-39.
44. Keefe RSE, Kraus MS. Measuring memory-prediction errors and their consequences in youth at risk for schizophrenia. Ann Acad Med Singapore 2009; 38: 414-16.
45. Javitt DC. When doors of perception close: bottom-up models of disrupted cognition in schizophrenia. Annu Rev Clin Psychol 2009; 5: 249-75.
46. Keefe RS, Perkins DO, Gu H, Zipursky RB, Christensen BK, Lieberman JA. A longitudinal study of neurocognitive function in individuals at-risk for psychosis. Schizophr Res 2006; 88: 26-35.
47. Pogge DL, Insalaco B, Bertisch H etal. Six-year outcomes in first admission adolescent inpatients: clinical and cognitive characteristics at admission as predictors. Psychiatry Res 2008; 160: 47-54.
48. Wright IC, Rabe-Hesketh S, Woodruff PW, David AS, Murray RM, Bullmore ET. Meta-analysis of regional brain volumes in schizophrenia. Am J Psychiatry 2000; 157: 16-25.
49. Shenton ME, Kikinis R, McCarley RW, Metcalf D, Tieman J, Jolesz FA. Application of automated MRI volumetric measurement techniques to the ventricular system in schizophrenics and normal controls. Schizophr Res 1991; 5: 103-13.
50. Kasai K, Shenton ME, Salisbury DF etal. Differences and similarities in insular and temporal pole MRI gray matter volume abnormalities in first-episode schizophrenia and affective psychosis. Arch Gen Psychiatry 2003; 60: 1069-77.
51. Fannon D, Chitris X, Doku V etal. Features of structural brain abnormality detected in first-episode psychosis. Am J Psychiatry 2000; 157: 1829-34.
52. Bachmann S, Bottmer C, Pantel J etal. MRI-morphometric changes in first-episode schizophrenic patients at 14months follow-up. Schizophr Res 2004; 67: 301-3.
53. Hietala J, Cannon TD, van Erp TGM. Regional brain morphology and duration of illness in never medicated first episode patients with schizophrenia. Schizophr Res 2003; 64: 79-81.
54. Joyal C. The amygdale and schizophrenia: a volumetric magnetic resonance imaging study in first-episode, neuroleptic-naïve patients. Biol Psychiatry 2003; 54: 1302-4.
55. Sumich A, Chitris XA, Fannon DG etal. Temporal lobe abnormalities in first episode psychosis. Am J Psychiatry 2002; 159: 1232-35.
56. Pantelis C, Velakoulis D, McGorry P. Neuroanatomical abnormalities before and after onset of psychosis. Lancet 2003; 361: 281-88.
57. Velakoulis D, Wood SJ, Wong MT etal. Hippocampal and amygdala volumes according to psychosis stage and diagnosis: a magnetic resonance imaging study of chronic schizophrenia, first-episode psychosis, and ultra-high-risk individuals. Arch Gen Psychiatry 2006; 63: 139-49.
58. Fusar-Poli P, Perez J, Broome M etal. Neurofunctional correlates of vulnerability to psychosis: a systematic review and meta-analysis. Neurosci Biobehav Rev 2007; 31: 465-84.
59. Goldstein JM, Goodman JM, Seidman LJ etal. Cortical abnormalities in schizophrenia identified by structural magnetic resonance imaging. Arch Gen Psychiatry 1999; 56: 537-47.
60. Narr KL, Thompson PM, Szeszko P etal. Regional specificity of hippocampal volume reductions in first-episode schizophrenia. Neuroimage 2004; 21: 1563-75.
61. Qiu A, Younes L, Wang L etal. Combining anatomical manifold information via diffeomophic metric mappings for studying cortical thinning of the cingulated gyrus in schizophrenia. Neuroimage 2007; 37: 821-33.
62. Borgwardt SJ, Riecher-Rössler A, Dazzan P etal. Regional gray matter volume abnormalities in the at risk mental state. Biol Psychiatry 2007; 61: 1148-56.
63. Sowell ER, Thompson PM, Tessner KD, Toga AW. Mapping continued brain growth and gray matter density reduction in dorsal frontal cortex: inverse relationships during postadolescent brain maturation. J Neurosci 2001; 21: 8819-29.
64. Sowell ER, Thompson PM, Leonard CM, Welcome SE, Kan E, Toga AW. Longitudinal mapping of cortical thickness and brain growth in normal children. J Neurosci 2004; 24: 8223-31.
65. 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 U S A 2001; 25: 11650-55.
66. Bush G, Luu P, Posner MI. Cognitive and emotional influences in anterior cingulate cortex. Trends Cogn Sci 2000; 4: 215-22.
67. Ridderinkhof KR, Ullsperger M, Crone EA, Nieuwenhuis S. The role of the medial frontal cortex in cognitive control. Science 2004; 306: 443-47.
68. Buckner RL, Kelley WM, Petersen SE. Frontal cortex contributes to human memory formation. Nat Neurosci 1999; 2: 311-14.
69. Curtis CE, D'Esposito M. Persistent interventions for schizophrenia vulnerability: the risk of being 'at risk'. Schizophr Res 2005; 73: 173-84.
70. Tan HY, Choo WC, Fones CSL, Chee MW. fMRI study of maintenance and manipulation processes within working memory in first-episode schizophrenia. Am J Psychiatry 2005; 162: 1849-58.
71. Mendrek A, Laurens KR, Kiehl KA, Ngan ET, Stip E, Liddle PF. Changes in distributed neural circuitry function in patients with first-episode schizophrenia. Br J Psychiatry 2004; 185: 205-14.
72. Snitz BE, MacDonald A III, Cohen JD, Cho RY, Becker T, Carter CS. Lateral and medial hypofrontality first-episode schizophrenia: functional activity in a medication-naïve state and effects of short-term atypical antipsychotic treatment. Am J Psychiatry 2005; 162: 2322-39.
73. Barch DM, Braver TS, Akbudak E, Conturo T, Ollinger J, Snyder A. Anterior cingulate cortex and response conflict: effects of response modality and processing domain. Cereb Cortex 2001; 11: 837-48.
74. MacDonald AW 3rd, Carter CS, Kerns JG etal. Specificity of prefrontal dysfunction and context processing deficits to schizophrenia in never-medicated patients with first-episode psychosis. Am J Psychiatry 2005; 162: 475-84.
75. Seidman LJ, Thermenos HW, Poldrack RA etal. Altered brain activation in dorsolateral prefrontal cortex in adolescents and young adults at genetic risk for schizophrenia: an fMRI study of working memory. Schizophr Res 2006; 85: 58-72.
76. Bowden NA, Weidenhofer J, Scott RJ etal. Preliminary investigation of gene expression profiles in peripheral blood lymphocytes in schizophrenia. Schizophr Res 2006; 82: 175-83.
77. Tsuang MT, Nossova N, Yager T etal. Assessing the validity of blood-based gene expression profiles for the classification of schizophrenia and bipolar disorder: a preliminary report. Am J Med Genet 2005; 133: 1-5.
78. Fenton WS, Hibbeln J, Knable M. Essential fatty acids, lipid membrane abnormalities, and the diagnosis and treatment of schizophrenia. Biol Psychiatry 2000; 47: 8-21.
79. Huang JT, Leweke FM, Oxley D etal. Disease biomarkers in cerebrospinal fluid of patients with first-on set psychosis. PLoS Med 2006; 11: 2145-58.
80. Keefe RS, Bilder RM, Davis SM etal. Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE Trial. Arch Gen Psychiatry 2007; 64: 633-47.
81. Davidson M, Galderisi S, Weiser M etal. Cognitive effects of antipsychotics drugs in first-episode schizophrenia and schizophreniform disorder: a randomized, open-label clinical trial (EUFEST). Am J Psychiatry 2009; 166: 675-82.
82. Green MF, Kern RS, Braff DL, Mintz J. Neurocognitive deficits and functional outcome in schizophrenia: are we measuring the 'right stuff'? Schizophr Bull 2000; 26: 119-36.
83. Harvey PD, Green MF, Keefe RSE, Velligan DI. Cognitive function in schizophrenia: its role in the definition and evaluation of effective treatments for the illness. J Clin Psychiatry 2004; 65: 361-72.
84. Buchanan RW, Davis M, Goff D etal. A summary of the FDA-NIMH-MATRICS workshop on clinical trial design for neurocognitive drugs for schizophrenia. Schizophr Bull 2005; 31: 5-19.
85. Flood JF, Morley JE, Roberts E. Memory-enhancing effects in male mice of pregnenolone and steroids metabolically derived from it. Proc Natl Acad Sci U S A 1992; 89: 1567-71.
86. Vallee M, Mayo W, Darnaudery M etal. Neurosteroids: deficient cognitive performance in aged rats depends on low pregnenolone sulfate levels in the hippocampus. Proc Natl Acad Sci U S A 1997; 94: 14865-70.
87. Vallee M, Purdy RH, Mayo W, Koob GF, Le Moal M. Neuroactive steroids: new biomarkers of cognitive aging. J Steroid Biochem Mol Biol 2003; 85: 329-35.
88. Flood JF, Morley JE, Roberts E. Pregnenolone sulfate enhances post-training memory processes when injected in very low doses into limbic system structures: the amygdala is by far the most sensitive. Proc Natl Acad Sci U S A 1995; 92: 10806-10.
89. Akwa Y, Ladurelle N, Covey DF, Baulieu EE. The synthetic enantiomer of pregnenolone sulfate is very active on memory in rats and mice, even more so than its physiological neurosteroid counterpart: distinct mechanisms? Proc Natl Acad Sci U S A 2001; 98: 14033-37.
90. Irwin RP, Lin SZ, Rogawski MA, Purdy RH, Paul SM. Steroid potentiation and inhibition of N-methyl-D-aspartate receptor-mediated intracellular Ca++ responses: structure-activity studies. J Pharmacol Exp Ther 1994; 271: 677-82.
91. Hakak Y, Walker JR, Li C etal. Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia. Proc Natl Acad Sci U S A 2001; 98: 4746-51.
92. Tkachev D, Mimmack ML, Ryan MM etal. Oligodendrocyte dysfunction in schizophrenia and bipolar disorder. Lancet 2003; 362: 798-805.
93. Ciriza I, Azcoitia I, Garcia-Segura LM. Reduced progesterone metabolites protect rat hippocampal neurones from kainic acid excitotoxicity in vivo. J Neuroendocrinol 2004; 16: 58-63.
94. Lockhart EM, Warner DS, Pearlstein RD, Penning DH, Mehrabani S, Boustany RM. Allopregnanolone attenuates N-methyl-D-aspartate-induced excitotoxicity and apoptosis in the human NT2 cell line in culture. Neurosci Lett 2002; 328: 33-6.
95. Javitt DC. Glutamate as a therapeutic target in psychiatric disorders. Mol Psychiatry 2004; 9: 984-97.
96. Millan MJ. N-Methyl-D-aspartate receptors as a target for improved antipsychotic agents: novel insights and clinical perspectives. Psychopharmacology 2005; 179: 30-53.
97. Sliwinski A, Monnet FP, Schumacher M, Morin-Surun MP. Pregnenolone sulfate enhances long-term potentiation in CA1 in rat hippocampus slices through the modulation of N-methyl-D-aspartate receptors. J Neurosci Res 2004; 78: 691-701.
98. Romeo E, Cheney DL, Zivkovic I, Costa E, Guidotti A. Mitochondrial diazepam-binding inhibitor receptor complex agonists antagonize dizocilpine amnesia: putative role for allopregnanolone. J Pharmacol Exp Ther 1994; 270: 89-96.
99. Mathis C, Vogel E, Cagniard B, Criscuolo F, Ungerer A. The neurosteroid pregnenolone sulfate blocks deficits induced by a competitive NMDA antagonist in active avoidance and lever-press learning tasks in mice. Neuropharmacology 1996; 35: 1057-64.
100. Darnaudery M, Pallares M, Piazza PV, Le Moal M, Mayo W. The neurosteroid pregnenolone sulfate infused into the medial septum nucleus increases hippocampal acetylcholine and spatial memory in rats. Brain Res 2002; 951: 237-42.
101. Darnaudery M, Koehl M, Pallares M, Le Moal M, Mayo W. The neurosteroid pregnenolone sulfate increases cortical acetylcholine release: a microdialysis study in freely moving rats. J Neurochem 1998; 71: 2018-22.
102. Kirkpatrick B, Fenton WS, Carpenter WT Jr, Marder SR. The NIMH-MATRICS consensus statement on negative symptoms. Schizophr Bull 2006; 32: 214-9.
103. Greenwood KE, Landau S, Wykes T. Negative symptoms and specific cognitive impairments as combined targets for improved functional outcome within cognitive remediation therapy. Schizophr Bull 2005; 31: 910-21.
104. Marx CE, Keefe R, Buchanan RW etal. Proof-of-concept trial with the neurosteroid pregnenolone targeting cognitive and negative symptoms in schizophrenia. Neuropsychopharmacology 2009; 34: 1885-903.
105. Davidson R, Koets P, Snow WG, Gabrielson LG. The effects of Delta 5 pregnenolone in rheumatoid arthritis. Arch Intern Med 1950; 85: 365-88.
106. 5-pregnenolone in various clinical disorders. J Clin Endocrinol Metab 1951; 11: 559-77.
107. Freeman H, Pincus G, Johnson CW, Bachrach S, McCabe GE, MacGilpin H. Therapeutic efficacy of Δ5 pregnenolone in rheumatoid arthritis. JAMA 1950; 142: 1124-27.
108. A receptor. Biochem Pharmacol 1995; 46: 1-16.