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  • Print publication year: 2010
  • Online publication date: May 2010

Chapter 13 - Genetic investigations in the CATIE sample

Summary

This chapter describes the cognitive findings from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project, including analyses of the baseline cognitive assessments in 1,331 patients, one of the largest schizophrenia cohorts to be studied with neuropsychological measures, and the effects of treatment on these measures in over 800 patients randomized to five different antipsychotic treatments. The choice of tests for a neurocognitive battery is often controversial. Since the CATIE project promised to yield a rich database, it is important that the batteries of tests chosen for the project receive consensus approval from the leaders in schizophrenia and dementia research. The aim of the CATIE Neurocognitive Assessment Unit training program is for testers and investigators to achieve thorough understanding of the rationale and methods of the neurocognitive assessment protocol, and considerable preparation preceded the production of manuals and training materials.

References

1. SullivanPF.Schizophrenia genetics: The search for a hard lead. Current Opinion in Psychiatry 2008;21:157–60.
2. SullivanPF, KendlerKS and NealeMC.Schizophrenia as a complex trait: Evidence from a meta-analysis of twin studies. Archives of General Psychiatry 2003;60:1187–92.
3. SullivanPF. The genetics of schizophrenia. PLoS Medicine 2005;2:e212.
4. LohmuellerKE, PearceCL, PikeM, LanderES and HirschhornJN. Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. Nature Genetics 2003;33:177–82.
5. IoannidisJP. Commentary: Grading the credibility of molecular evidence for complex diseases. International Journal of Epidemiology 2006;35:572–8; discussion 593–6.
6. LewisCM, LevinsonDF, WiseLH, et al. Genome scan meta-analysis of schizophrenia and bipolar disorder. II: Schizophrenia. American Journal of Human Genetics 2003;73:34–48.
7. LiD, CollierDA and HeL. Meta-analysis shows strong positive association of the neuregulin 1 (NRG1) gene with schizophrenia. Human Molecular Genetics 2006;15:1995–2002.
8. StefanssonH, SigurdssonE, SteinthorsdottirV, et al. Neuregulin 1 and susceptibility to schizophrenia. American Journal of Human Genetics 2002;71:877–92.
9. StraubRE, JiangY, MacLeanCJ, et al. Genetic variation in the 6p22.3 gene DTNBP1, the human ortholog of the mouse dysbindin gene, is associated with schizophrenia. American Journal of Human Genetics 2002;71:337–48.
10. MillarJK, Wilson-AnnanJC, AndersonS, et al. Disruption of two novel genes by a translocation co-segregating with schizophrenia. Human Molecular Genetics 2000;9:1415–23.
11. FraylingTM, TimpsonNJ, WeedonMN, et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 2007;316:889–94.
12. RischN and MerikangasK. The future of genetic studies of complex human diseases. Science 1996;273:1516–7.
13. FraylingTM. Genome-wide association studies provide new insights into type 2 diabetes aetiology. Nature Reviews. Genetics 2007;8:657–62.
14. SullivanPF, LinD, TzengJY, et al. Genomewide association for schizophrenia in the CATIE study: Results of stage 1. Molecular Psychiatry 2008;13:570–84.
15. LenczT, MorganTV, AthanasiouM, et al. Converging evidence for a pseudoautosomal cytokine receptor gene locus in schizophrenia. Molecular Psychiatry 2007;12:572–80.
16. KirovG, ZaharievaI, GeorgievaL, et al. A genome-wide association study in 574 schizophrenia trios using DNA pooling. Molecular Psychiatry 2009;14:796–803.
17. ShifmanS, JohannessonM, BronsteinM, et al. Genome-wide association identifies a common variant in the reelin gene that increases the risk of schizophrenia only in women. PLoS Genetics 2008;4:e28.
18. StroupTS, McEvoyJP, SwartzMS, et al. The National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project: Schizophrenia trial design and protocol development. Schizophrenia Bulletin 2003;29:15–31.
19. LiebermanJA, StroupTS, McEvoyJP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. New England Journal of Medicine 2005;353:1209–23.
20. KaySR, FiszbeinA and OplerLA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin 1987;13:261–76.
21. SullivanPF, KeefeRS, LangeLA, et al. NCAM1 and neurocognition in schizophrenia. Biological Psychiatry 2007;61:902–10.
22. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994.
23. FirstMB, SpitzerRL, GibbonM and WilliamsJBW. Structured Clinical Interview for DSM-IV Axis I Disorders–Administration Booklet. Washington DC: American Psychiatric Press Inc; 1994.
24. SkellyT, PinheiroAP, LangeLAand Sullivan PF. Is rs7566605, a SNP near INSIG2, associated with body mass in a randomized clinical trial of antipsychotics in schizophrenia? Molecular Psychiatry 2007;12:321–2.
25. HerbertA, GerryNP, McQueenMB, et al. A common genetic variant is associated with adult and childhood obesity. Science 2006;312:279–83.
26. PinheiroAP, KeefeRS, SkellyT, et al. AKT1 and neurocognition in schizophrenia. The Austrailian and New Zealand Journal of Psychiatry 2007;41:169–77.
27. CampbellDB, EbertPJ, SkellyT, et al. Ethnic stratification of the association of RGS4 variants with antipsychotic treatment response in schizophrenia. Biological Psychiatry 2008;63:32–41.
28. CampbellDB, LangeLA, SkellyT, LiebermanJ, LevittP and SullivanPF. Association of RGS2 and RGS5 variants with schizophrenia symptom severity. Schizophrenia Research 2008;101:67–75.
29. CrowleyJJ, KeefeRS, PerkinsDO, StroupTS, LiebermanJA and SullivanPF.The neuregulin 1 promoter polymorphism rs6994992 is not associated with chronic schizophrenia or neurocognition. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 2008;147B:1298–300.
30. HallJ, WhalleyHC, JobDE, et al. A neuregulin 1 variant associated with abnormal cortical function and psychotic symptoms. Nature Neuroscience 2006;9:1477–8.
31. LawAJ, LipskaBK, WeickertCS, et al. Neuregulin 1 transcripts are differentially expressed in schizophrenia and regulated by 5′ SNPs associated with the disease. Proceedings of the National Academy of Sciences of the United States of America 2006;103:6747–52.
32. Grossman I SullivanPF, WalleyN, et al. Genetic determinants of variable metabolism have little impact on the clinical use of leading antipsychotics in the CATIE study. Genetics in Medicine 2008;10:720–9.
33. PritchardJK, StephensM, RosenbergNA and DonnellyP. Association mapping in structured populations. American Journal of Human Genetics 2000;67:170–81.
34. BaldingDJ. A tutorial on statistical methods for population association studies. Nature Reviews. Genetics 2006;7:781–91.
35. MahS, NelsonMR, DelisiLE, et al. Identification of the semaphorin receptor PLXNA2 as a candidate for susceptibility to schizophrenia. Molecular Psychiatry 2006;11:471–8.
36. HennahW, VariloT, KestilaM, et al. Haplotype transmission analysis provides evidence of association for DISC1 to schizophrenia and suggests sex-dependent effects. Human Molecular Genetics 2003;12:3151–9.
37. CannonTD, HennahW, van ErpTG, et al. Association of DISC1/TRAX haplotypes with schizophrenia, reduced prefrontal gray matter, and impaired short- and long-term memory. Archives of General Psychiatry 2005;62:1205–13.
38. ShifmanS, BronsteinM, SternfeldM, et al. A highly significant association between a COMT haplotype and schizophrenia. American Journal of Human Genetics 2002;71:1296–302.
39. ManolioTA, RodriguezLL, BrooksL, et al. New models of collaboration in genome-wide association studies: The Genetic Association Information Network. Nature Genetics 2007;39:1045–51.
40. BarrettJC and CardonLR. Evaluating coverage of genome-wide association studies. Nature Genetics 2006;38:659–62.
41. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 2007;447:661–78.
42. SullivanPF. Spurious genetic associations. Biological Psychiatry 2007;61:1121–16.
43. McClellanJM, SusserE and KingMC.Schizophrenia: A common disease caused by multiple rare alleles. Br J Psychiatry 2007;190:194–9.