The importance of endophenotypes in schizophrenia research

Schizophrenia Research

Volumn 163, Issue 1-3, 2015, Pages 1-8

  Braff, David L ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CASE CONTROL STUDY; COGNITIVE DEFECT; COHORT ANALYSIS; DISEASE CLASSIFICATION; EDITORIAL; ENDOPHENOTYPE; FIRST DEGREE RELATIVE; FOLLOW UP; FUNCTIONAL DISEASE; GENE REGULATORY NETWORK; GENE SEQUENCE; GENETIC ASSOCIATION; GENETIC LINKAGE; GENETIC RISK; HERITABILITY; HUMAN; INFORMATION PROCESSING; MEDICAL RESEARCH; NEUROPHYSIOLOGY; PATIENT SELECTION; POPULATION SIZE; PRIORITY JOURNAL; QUANTITATIVE ANALYSIS; SCHIZOPHRENIA; STEM CELL TRANSPLANTATION; TREATMENT INDICATION; FAMILY; GENETIC PREDISPOSITION; GENETICS; MULTICENTER STUDY (TOPIC); PATHOPHYSIOLOGY;

ENDOPHENOTYPES; FAMILY; GENETIC PREDISPOSITION TO DISEASE; HUMANS; MULTICENTER STUDIES AS TOPIC; SCHIZOPHRENIA;

EID: 84925869807     PISSN: 09209964     EISSN: 15732509     Source Type: Journal    
DOI: 10.1016/j.schres.2015.02.007     Document Type: Editorial

References (59)

1. Barrett J.E., Coyle J.T. Summary and perspectives: neurological and neurodevelopmental disorders and regulation of epigenetic changes. Translational Neuroscience: Applications in Neurology, Psychiatry and Neurodevelopmental Disorders 2012, 334-338. Cambridge University Press, Cambridge. J.E. Barrett, J.T. Coyle, M. Williams (Eds.).
2. Bleuler E. Dementia praecox, oder Gruppe der Schizophrenien 1911, Deuticke, F, Leipzig.
3. Braff D.L. Promises, challenges and caveats of translational research in neuropsychiatry. Translational Neuroscience: Applications in Neurology, Psychiatry, and Neurodevelopmental Disorders 2012, 339-358. Cambridge University Press, Cambridge. J.E. Barrett, J.T. Coyle, M. Williams (Eds.).
4. Braff L., Braff D.L. The neuropsychiatric translational revolution: still very early and still very challenging. JAMA Psychiatry 2013, 70(8):777-779.
5. Braff D.L., Freedman R. Clinically responsible genetic testing in neuropsychiatric patients: a bridge too far and too soon. Am. J. Psychiatry 2008, 165(8):952-955.
6. Braff D.L., Freedman R., Schork N.J., Gottesman I.I. Deconstructing schizophrenia: an overview of the use of endophenotypes in order to understand a complex disorder. Schizophr. Bull. 2007, 33(1):21-32.
7. Braff D.L., Geyer M.A., Swerdlow N.R. Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies. Psychopharmacology 2001, 156(2-3):234-258.
8. Braff D.L. Genomic substrates of neurophysiological endophenotypes: where we've been and where we're going. Psychophysiology 2014, 51(12):1323-1324. (Dec).
9. Brennand K.J., Simone A., Tran N., Gage F.H. Modeling psychiatric disorders at the cellular and network levels. Mol. Psychiatry 2012, 17(12):1239-1253.
10. Calkins M.E., Dobie D.J., Cadenhead K.S., Olincy A., Freedman R., Green M.F., Greenwood T.A., Gur R.E., Gur R.C., Light G.A., Mintz J., Nuechterlein K.H., Radant A.D., Schork N.J., Seidman L.J., Siever L.J., Silverman J.M., Stone W.S., Swerdlow N.R., Tsuang D.W., Tsuang M.T., Turetsky B.I., Braff D.L. The Consortium on the Genetics of Endophenotypes in Schizophrenia: model recruitment, assessment, and endophenotyping methods for a multisite collaboration. Schizophr. Bull. 2007, 33(1):33-48.
11. Fisher M., Holland C., Subramaniam K., Vinogradov S. Neuroplasticity-based cognitive training in schizophrenia: an interim report on the effects 6months later. Schizophr. Bull. 2010, 36(4):869-879.
12. Flint J., Timpson N., Munafo M. Assessing the utility of intermediate phenotypes for genetic mapping of psychiatric disease. Trends Neurosci. 2014, (pii: S0166-2236(14)00150-7, Epub ahead of print, Sept. 9). 10.1016/j.tins.2014.08.007.
13. Geyer M.A., Krebs-Thomson K., Braff D.L., Swerdlow N.R. Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review. Psychopharmacology 2001, 156(2-3):117-154.
14. Glahn D.C., Curran J.E., Winkler A.M., Carless M.A., Kent J.W. Jr, Charlesworth J.C., Johnson M.P., Goring H.H.H., Cole S.A., dyer T.D., Moses E.K., Olvera R.L., Kochunov P., Duggirala R., Fox P.T., Almasy L., Blangero J. High dimensional endophenotype ranking in the search for major depression risk genes. Biol. Psychiatry 2012, (71):6-14.
15. Glahn D.C., Knowles E.E.M., McKay D.R., Sprooten E., Raventos H., Blangero J., Gottesman I.I., Almasy L. Arguments for the sake of endophenotypes: examining common misconceptions about the use of endophenotypes in psychiatric genetics. Am. J. Med. Genet. B 2014, (9999):1-9.
16. Goff D.C. Bitopertin: the good news and bad news. JAMA Psychiatry 2014, 10.1001/jamapsychiatry.2014.257.
17. Goldstein D.B. Common genetic variation and human traits. N. Engl. J. Med. 2009, 360(17):1696-1698.
18. Gottesman I.I., Gould T.D. The endophenotype concept in psychiatry: etymology and strategic intentions. Am. J. Psychiatry 2003, 160(4):636-645.
19. Gottesman I.I., Shields J. Genetic theorizing and schizophrenia. Br. J. Psychiatry 1973, 122(566):15-30.
20. Green M.F., Nuechterlein K.H., Gold J.M., Barch D., Cohen J., Essock S., Fenton W.S., Frese F., Goldberg T.E., Heaton R.K., Keefe R.S.E., Kern R.S., Kraemer H., Stover E., Weinberger D.R., Zalcman S., Marder S.R. Approaching a consensus cognitive battery for clinical trials in schizophrenia: the NIMH-MATRICS conference to select cognitive domains and test criteria. Biol. Psychiatry 2004, 56(5):301-307.
21. Green M.F., Schooler N.R., Kern R.S., Frese F.J., Granberry W., Harvey P.D., Karson C.N., Peters N., Stewart M., Seidman L.J., Sonnenberg J., Stone W.S., Walling D., Stover E., Marder S.R. Evaluation of functionally meaningful measures for clinical trials of cognition enhancement in schizophrenia. Am. J. Psychiatry 2011, 168(4):400-407.
22. Greenwood T.A., Braff D.L., Light G.A., Cadenhead K.S., Calkins M.E., Dobie D.J., Freedman R., Green M.F., Gur R.E., Gur R.C., Mintz J., Nuechterlein K.H., Olincy A., Radant A.D., Seidman L.J., Siever L.J., Silverman J.M., Stone W.S., Swerdlow N.R., Tsuang D.W., Tsuang M.T., Turetsky B.I., Schork N.J. Initial heritability analyses of endophenotypic measures for schizophrenia: the consortium on the genetics of schizophrenia. Arch. Gen. Psychiatry 2007, 64(11):1242-1250.
23. Greenwood T.A., Lazzeroni L.C., Murray S.S., Cadenhead K.S., Calkins M.E., Dobie D.J., Green M.F., Gur R.E., Gur R.C., Hardiman G., Kelsoe J.R., Leonard S., Light G.A., Neuchterlein K.H., Olincy A., Radant A.D., Schork N.J., Seidman L.J., Siever L.J., Silverman J.M., Stone W.S., Swerdlow N.R., Tsuang D.W., Turetsky B.I., Freedman R., Braff D.L. Analysis of 94 candidate genes and 12 endophenotypes for schizophrenia from the Consortium on the Genetics of Schizophrenia. Am. J. Psychiatry 2011, 168(9):930-946.
24. Greenwood T.A., Light G.A., Swerdlow N.R., Radant A.D., Braff D.L. Association analysis of 94 candidate genes and schizophrenia-related endophenotypes. PLoS One 2012, 7(1):e29630. 10.1371/journal.pone.0029630.
25. Greenwood T.A., Swerdlow N.R., Gur R.E., Cadenhead K.S., Calkins M.E., Dobie D.J., Freedman R., Green M.F., Gur R.C., Lazzeroni L.C., Nuechterlein K.H., Olincy A., Radant A.D., Ray A., Schork N.J., Seidman L.J., Siever L.J., Silverman J.M., Stone W.S., Sugar C.A., Tsuang D.W., Tsuang M.T., Turetsky B.I., Light G.A., Braff D.L. Genome-wide linkage analyses of 12 endophenotypes for schizophrenia from the Consortium on the Genetics of Schizophrenia. Am. J. Psychiatry 2013, 170(5):521-532.
26. Gulsuner S., Wash T., Watts A.C., Lee M.K., Thornton A.M., Casadei S., Rippey C., Shahin H., Consortium on the Genetics of Schizophrenia (COGS), PAARTNERS Study Group, Nimgaonkar V.L., Go R.C.P., Savage R.M., Swerdlow N.R., Gur R.E., Braff D.L., King M.C., McClellan J.M. Spatial and temporal mapping of de novo mutations in schizophrenia to a fetal prefrontal cortical network 2013, 154(3):518-529.
27. Insel T.R., Cuthbert B.N. Endophenotypes: bridging genomic complexity and disorder heterogeneity. Biol. Psychiatry 2009, 66(11):988-989.
28. Javitt D.C. Twenty-five years of glutamate in schizophrenia: are we there yet?. Schizophr. Bull. 2012, 38(5):911-913.
29. Karayiorgou M., Flint J., Gogos J.A., Malenka R.C., the Genetic and Neural Complexity in Psychiatry 2011 Working Group The best of times, the worst of times for psychiatric disease. Nat. Neurosci. 2012, 15(6):811-812.
30. Kuhn T. The Structure of Scientific Revolutions 1962, University of Chicago Press, Chicago.
31. Lazzeroni L.C., Lu Y., Belitskaya-Levy I. P-values in genomics: apparent precision masks high uncertainty. Mol. Psychiatry 2014, (Epub ahead of print Jan. 14). 10.1038/mp.2013.184.
32. Lazzeroni L.C., Ray A. The cost of large numbers of hypothesis tests on power, effect size and sample. Mol. Psychiatry 2010, (17):108-114.
33. Lee J., Green M.F., Calkins M.E., Greenwood T.A., Gur R.E., Gur R.C., Lazzeroni L.C., Light G.A., Nuechterlein K.H., Radant A.D., Seidman L.J., Siever L.J., Silverman J.M., Sprock J., Stone W.S., Sugar C.A., Swerdlow N.R., Tsuang D.W., Tsuang M.T., Turetsky B.I., Braff D.L. Verbal working memory in schizophrenia from the Consortium on the Genetics of Schizophrenia (COGS) Study: The moderating role of smoking status and antipsychotic medications. Schizophr Res 2015, 163(1-3):24-31. (in this issue).
34. Light G.A., Braff D.L. Stability of mismatch negativity deficits and their relationship to functional impairments in chronic schizophrenia. Am. J. Psychiatry 2005, 162(9):1741-1743.
35. Light G.A., Greenwood T.A., Swerdlow N.R., Calkins M.E., Freedman R., Green M.F., Gur R.E., Gur R.C., Lazzeroni L.C., Nuechterlein K.H., Olincy A., Radant A.D., Seidman L.J., Siever L.J., Silverman J.M., Sprock J., Stone W.S., Sugar C.A., Tsuang D.W., Tsuang M.T., Turetsky B.I., Braff D.L. Comparison of the heritability of schizophrenia and endophenotypes in the COGS-1 family study. Schizophr. Bull. 2014, 40(6):1404-1411.
36. Light G.A., Swerdlow N.R., Thomas M.L., Calkins M.E., Green M.F., Greenwood T.A., Gur R.E., Gur R.C., Lazzeroni L.C., Nuechterlein K.H., Pela M., Radant A.D., Seidman L.J., Sharp R.F., Siever L.J., Silverman J.M., Sprock J., Stone W.S., Sugar C.A., Tsuang D.W., Tsuang M.T., Braff D.L., Turetsky B.I. Validation of mismatch negativity and P3a for use in multi-site studies of schizophrenia: Characterization of demographic, clinical, cognitive, and functional correlates in COGS-2. Schizophr Res 2015, 163(1-3):63-72. (in this issue).
37. Malone S.M., Burwell S.J., Vaidyanathan U., Miller M.B., McGue M., Iacono W.G. Heritability and molecular-genetic basis of resting EEG activity: a genome-wide association study. Psychophysiology. Psychophysiology 2014, 51(12):1225-1245.
38. National Research Council Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease 2011, The National Academies Press, Washington, DC.
39. Nuechterlein K.H., Green M.F., Kern R.S., Baade L.E., Barch D.M., Cohen J.D., Essock S., Fenton W.S., Frese F.J., Gold J.M., Goldberg T., Heaton R.K., Keefe R.S.E., Kraemer H., Mesholam-Gately R., Seidman L.J., Stover E., Weinberger D., Young A.S., M.S.H.S., Zalcman S., Marder S.R. The MATRICS consensus cognitive battery: part 1. Test selection, reliability, and validity. Am. J. Psychiatry 2008, 165(2):203-213.
40. Owen M.J., Craddock N., O'Donovan M.C. Suggestion of roles for both common and rare risk variants in genome-wide studies of schizophrenia. Arch. Gen. Psychiatry 2010, 67(7):667-673.
41. Ripke S., O'Dushlaine C., Chambert K. Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Nat. Genet. 2013, 45(10):1150-1159.
42. Roffman J.L., Brohawn D.G., Nitenson A.Z., Macklin E.A., Smoller J.W., Goff D.C. Genetic variation throughout the folate metabolic pathway influences negative symptom severity in schizophrenia. Schizophr. Bull. 2013, 39(2):330-338.
43. Schork N.J., Greenwood T.A., Braff D.L. Statistical genetics concepts and approaches in schizophrenia and related neuropsychiatric research. Schizophr. Bull. 2007, 33(1):95-104.
44. Schizophrenia Working Group of the Psychiatric Genomics Consortium Biological insights from 108 schizophrenia-associated genetic loci. Nature 2014, 511:421-427.
45. Stoner R., Chow M.L., Boyle M.P., Sunkin S.M., Mouton P.R., Roy S., Wynshaw-Boris A., Colamarino S.A., Lein E.S., Courchesne E. Patches of disorganization in the neocortex of children with autism. N. Engl. J. Med. 2014, 370(13):1209-1219.
46. Swerdlow N.R. Are we studying and treating schizophrenia correctly?. Schizophr. Res. 2011, 130(1-3):1-10.
47. Swerdlow N.R., Geyer M.A., Braff D.L. Neural circuit regulation of prepulse inhibition of startle in the rat: current knowledge and future challenges. Psychopharmacology (Berl.) 2001, 156(2-3):194-215.
48. Swerdlow N.R., Light G.A., Sprock J., Calkins M.E., Green M.F., Greenwood T.A., Gur R.E., Gur R.C., Lazzeroni L.C., Nuechterlein K.H., Radant A.D., Ray A., Seidman L.J., Siever L.J., Silverman J.M., Stone W.S., Sugar C.A., Tsuang D.W., Tsuang M.T., Turestsky B.I., Braff D.L. Deficient prepulse inhibition in schizophrenia detected by the multi-site Consortium on the Genetics in Schizophrenia. Schizophr. Res. 2014, 152(2-3):503-512.
49. Swerdlow N.R., Gur R.E., Braff D.L. Consortium on the Genetics of Schizophrenia (COGS) assessment of endophenotypes for schizophrenia: An introduction to this Special Issue of schizophrenia research. Schizophr Res 2015, 163(1-3):9-16. (in this issue).
50. Tan H.Y., Callicott J.H., Weinberger D.R. Intermediate phenotypes in schizophrenia genetics redux: is it a no brainer?. Mol. Psychiatry 2008, 13(3):233-238.
51. Turetsky B.I., Dress E.M., Braff D.L., Calkins M.E., Green M.F., Greenwood T.A., Gur R.E., Gur R.C., Lazzeroni L.C., Nuechterlein K.H., Radant A.D., Seidman L.J., Siever L.J., Silverman J.M., Sprock J., Stone W.S., Sugar C.A., Swerdlow N.R., Tsuang D.W., Tsuang M.T., Light G. The utility of P300 as a schizophrenia endophenotype and predictive biomarker: Clinical and socio-demographic modulators in COGS-2. Schizophr Res 2015, 163(1-3):53-62. (in this issue).
52. Umbricht D., Alberati D., Martin-Facklam M., Borroni E., Youssef E.A., Ostland M., Wallace T.L., Knoflach F., Dorflinger E., Wettstein J.G., Bausch A., Garibaldi G., Santarelli L. Effect of bitopertin, a glycine reuptake inhibitor, on negative symptoms of schizophrenia: a randomized, double-blind, proof-of-concept study. JAMA Psychiatry 2014, 71(6):637-646. 10.1001/jamapsychiatry.2014.163.
53. Useem J. Business school, disrupted 2014, New York Times.
54. Vaidyanathan U., Malone S.M., Donnelly J.M., Hammer M.A., Miller M.B., McGue M., Iacono W.G. Heritability and molecular genetic basis of antisaccade eye tracking error rate: a genome-wide association study. Psychophysiology 2014, 51(12):1272-1284.
55. Vaidyanathan U., Malone S.M., Miller M.B., McGue M., Iacono W.G. Heritability and molecular genetic basis of acoustic startle eye blink and affectively modulated startle response: a genome-wide association study. Psychophysiology 2014, 51(12):1285-1299.
56. Watson J.D., Crick F.H.C. Molecular structure of nucleic acids: a structure for deoxyribose nucleic acid. Nature 1953, 171(4356):737-738.
57. Watson J.D., Crick F.H.C. Genetical implications of the structure of deoxyribonucleic acid. Nature 1953, 171(4361):964-967.
58. Williams M., Coyle J.T. Historical perspectives on the discovery and development of drugs to treat neurological disorders. Translational Neuroscience: Applications in Neurology, Psychiatry and Neurodevelopmental Disorders 2012, 129-148. Cambridge University Press, Cambridge. J.E. Barrett, J.T. Coyle, M. Williams (Eds.).
59. Wray N.R., Gottesman I.I. Using summary data from the Danish national registers to estimate heritabilities for schizophrenia, bipolar disorder, and major depressive disorder. Front. Genet. 2012, 3:118.