Hostname: page-component-78c5997874-j824f Total loading time: 0 Render date: 2024-11-19T08:20:37.439Z Has data issue: false hasContentIssue false
  • English
  • Français

Do COMT, BDNF and NRG1 polymorphisms influence P50 sensory gating in psychosis?

Published online by Cambridge University Press:  27 January 2010

M. Shaikh ,
M.-H. Hall ,
K. Schulze ,
A. Dutt ,
M. Walshe ,
I. Williams ,
M. Constante ,
M. Picchioni ,
T. Toulopoulou  and
D. Collier
...Show all authors
M. Shaikh*
Affiliation:
NIHR Biomedical Research Centre, Institute of Psychiatry, King's College London/South London and Maudsley NHS Foundation Trust, London, UK
M.-H. Hall
Affiliation:
Psychology Research Laboratory, Harvard Medical School, McLean Hospital, Belmont, MA, USA
K. Schulze
Affiliation:
NIHR Biomedical Research Centre, Institute of Psychiatry, King's College London/South London and Maudsley NHS Foundation Trust, London, UK
A. Dutt
Affiliation:
NIHR Biomedical Research Centre, Institute of Psychiatry, King's College London/South London and Maudsley NHS Foundation Trust, London, UK
M. Walshe
Affiliation:
NIHR Biomedical Research Centre, Institute of Psychiatry, King's College London/South London and Maudsley NHS Foundation Trust, London, UK
I. Williams
Affiliation:
NIHR Biomedical Research Centre, Institute of Psychiatry, King's College London/South London and Maudsley NHS Foundation Trust, London, UK
M. Constante
Affiliation:
NIHR Biomedical Research Centre, Institute of Psychiatry, King's College London/South London and Maudsley NHS Foundation Trust, London, UK
M. Picchioni
Affiliation:
NIHR Biomedical Research Centre, Institute of Psychiatry, King's College London/South London and Maudsley NHS Foundation Trust, London, UK St Andrew's Academic Centre, King's College London, Institute of Psychiatry, Northampton, UK
T. Toulopoulou
Affiliation:
NIHR Biomedical Research Centre, Institute of Psychiatry, King's College London/South London and Maudsley NHS Foundation Trust, London, UK
D. Collier
Affiliation:
NIHR Biomedical Research Centre, Institute of Psychiatry, King's College London/South London and Maudsley NHS Foundation Trust, London, UK
F. Rijsdijk
Affiliation:
MRC Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, London, UK
J. Powell
Affiliation:
NIHR Biomedical Research Centre, Institute of Psychiatry, King's College London/South London and Maudsley NHS Foundation Trust, London, UK
M. Arranz
Affiliation:
NIHR Biomedical Research Centre, Institute of Psychiatry, King's College London/South London and Maudsley NHS Foundation Trust, London, UK
R. M. Murray
Affiliation:
NIHR Biomedical Research Centre, Institute of Psychiatry, King's College London/South London and Maudsley NHS Foundation Trust, London, UK
E. Bramon
Affiliation:
NIHR Biomedical Research Centre, Institute of Psychiatry, King's College London/South London and Maudsley NHS Foundation Trust, London, UK
*
*Address for correspondence: Ms. M. Shaikh, Division of Psychological Medicine and Psychiatry, P063, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK. (Email: Madiha.Shaikh@kcl.ac.uk)
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Auditory P50 sensory gating deficits correlate with genetic risk for schizophrenia and constitute a plausible endophenotype for the disease. The well-supported role of catechol-O-methyltransferase (COMT), brain-derived neurotrophic factor (BDNF) and neuregulin 1 (NRG1) genes in neurodevelopment and cognition make a strong theoretical case for their influence on the P50 endophenotype.

Method

The possible role of NRG1, COMT Val158Met and BDNF Val66Met gene polymorphisms on the P50 endophenotype was examined in a large sample consisting of psychotic patients, their unaffected relatives and unrelated healthy controls using linear regression analyses.

Results

Although P50 deficits were present in patients and their unaffected relatives, there was no evidence for an association between NRG1, COMT Val158Met or BDNF Val66Met genotypes and the P50 endophenotype.

Conclusions

The evidence from our large study suggests that any such association between P50 indices and NRG1, COMT Val158Met or BDNF Val66Met genotypes, if present, must be very subtle.

Keywords

BDNFCOMTNRG1psychosisP50
Type
Original Articles
Information
Psychological Medicine , Volume 41 , Issue 2 , February 2011 , pp. 263 - 276
Copyright
Copyright © Cambridge University Press 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Adler, LE, Pachtman, E, Franks, RD, Pecevich, M, Waldo, MC, Freedman, R (1982). Neurophysiological evidence for a defect in neuronal mechanisms involved in sensory gating in schizophrenia. Biological Psychiatry 17, 639–654.Google Scholar
Altar, CA, Cai, N, Bliven, T, Juhasz, M, Conner, JM, Acheson, AL, Lindsay, RM, Wiegand, SJ (1997). Anterograde transport of brain-derived neurotrophic factor and its role in the brain. Nature 389, 856–860.CrossRefGoogle ScholarPubMed
Baker, N, Staunton, M, Adler, L, Gerhardt, G, Drebing, C, Waldo, M, Nagamoto, H, Freedman, R (1990). Sensory gating deficits in psychiatric inpatients: relation to catecholamine metabolites in different diagnostic groups. Biological Psychiatry 27, 519–528.Google Scholar
Blackwood, DH, Fordyce, A, Walker, MT, St Clair, DM, Porteous, DJ, Muir, WJ (2001). Schizophrenia and affective disorders – cosegregation with a translocation at chromosome 1q42 that directly disrupts brain-expressed genes: clinical and P300 findings in a family. American Journal of Human Genetics 69, 428–433.CrossRefGoogle ScholarPubMed
Braff, DL, Freedman, R, Schork, NJ, Gottesman, II (2007). Deconstructing schizophrenia: an overview of the use of endophenotypes in order to understand a complex disorder. Schizophrenia Bulletin 33, 21–32.CrossRefGoogle ScholarPubMed
Bramon, E, Dempster, E, Frangou, S, McDonald, C, Schoenberg, P, MacCabe, JH, Walshe, M, Sham, P, Collier, D, Murray, RM (2006). Is there an association between the COMT gene and P300 endophenotypes? European Psychiatry 21, 70–73.CrossRefGoogle ScholarPubMed
Bramon, E, Dempster, E, Frangou, S, Shaikh, M, Walshe, M, Filbey, FM, McDonald, C, Sham, P, Collier, DA, Murray, R (2008). Neuregulin-1 and the P300 waveform – a preliminary association study using a psychosis endophenotype. Schizophrenia Research 103, 178–185.Google Scholar
Cannon, TD, Keller, MC (2006). Endophenotypes in the genetic analyses of mental disorders. Annual Review of Clinical Psychology 2, 267–290.Google Scholar
Chen, QY, Chen, Q, Feng, GY, Wan, CL, Lindpaintner, K, Wang, LJ, Chen, ZX, Gao, ZS, Tang, JS, Li, XW, He, L (2006). Association between the brain-derived neurotrophic factor (BDNF) gene and schizophrenia in the Chinese population. Neuroscience Letters 397, 285–290.Google Scholar
Chen, YJ, Johnson, MA, Lieberman, MD, Goodchild, RE, Schobel, S, Lewandowski, N, Rosoklija, G, Liu, RC, Gingrich, JA, Small, S, Moore, H, Dwork, AJ, Talmage, DA, Role, LW (2008). Type III neuregulin-1 is required for normal sensorimotor gating, memory-related behaviors, and corticostriatal circuit components. Journal of Neuroscience 28, 6872–6883.CrossRefGoogle ScholarPubMed
Chen, ZY, Patel, PD, Sant, G, Meng, CX, Teng, KK, Hempstead, BL, Lee, FS (2004). Variant brain-derived neurotrophic factor (BDNF) (Met66) alters the intracellular trafficking and activity-dependent secretion of wild-type BDNF in neurosecretory cells and cortical neurons. Journal of Neuroscience 24, 4401–4411.Google Scholar
Clementz, B, Geyer, M, Braff, D (1998 a). Poor P50 suppression among schizophrenia patients and their first-degree biological relatives. American Journal of Psychiatry 155, 1691–1694.CrossRefGoogle ScholarPubMed
Clementz, BA, Geyer, MA, Braff, DL (1997). P50 suppression among schizophrenia and normal comparison subjects: a methodological analysis. Biological Psychiatry 41, 1035–1044.CrossRefGoogle ScholarPubMed
Clementz, BA, Geyer, MA, Braff, DL (1998 b). Multiple site evaluation of P50 suppression among schizophrenia and normal comparison subjects. Schizophrenia Research 30, 71–80.CrossRefGoogle ScholarPubMed
Cohen, J (1969). Statistical Power Analysis for the Behavioral Sciences. Academic Press: New York.Google Scholar
Corfas, G, Roy, K, Buxbaum, J (2004). Neuregulin 1-erbB signaling and the molecular/cellular basis of schizophrenia. Nature Neuroscience 7, 575–580.Google Scholar
Craddock, N, Dave, S, Greening, J (2001). Association studies of bipolar disorder. Bipolar Disorder 3, 284–298.CrossRefGoogle ScholarPubMed
Craddock, N, O'Donovan, MC, Owen, MJ (2006). Genes for schizophrenia and bipolar disorder? Implications for psychiatric nosology. Schizophrenia Bulletin 32, 9–16.CrossRefGoogle ScholarPubMed
Crowley, JJ, Keefe, RS, Perkins, DO, Stroup, TS, Lieberman, JA, Sullivan, PF (2008). The neuregulin 1 promoter polymorphism rs6994992 is not associated with chronic schizophrenia or neurocognition. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 147B, 1298–1300.Google Scholar
Dempster, E, Toulopoulou, T, McDonald, C, Bramon, E, Walshe, M, Filbey, F, Wickham, H, Sham, PC, Murray, RM, Collier, DA (2005). Association between BDNF val66 met genotype and episodic memory. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 134B, 73–75.Google Scholar
Durany, N, Michel, T, Zochling, R, Boissl, KW, Cruz-Sanchez, FF, Riederer, P, Thome, J (2001). Brain-derived neurotrophic factor and neurotrophin 3 in schizophrenic psychoses. Schizophrenia Research 52, 79–86.CrossRefGoogle ScholarPubMed
Dutt, A, McDonald, C, Dempster, E, Prata, D, Shaikh, M, Williams, I, Schulze, K, Marshall, N, Walshe, M, Allin, M, Collier, D, Murray, R, Bramon, E (2009). The effect of COMT, BDNF, 5-HTT, NRG1 and DTNBP1 genes on hippocampal and lateral ventricular volume in psychosis. Psychological Medicine 39, 1783–1797.CrossRefGoogle ScholarPubMed
Egan, MF, Goldberg, TE, Kolachana, BS, Callicott, JH, Mazzanti, CM, Straub, RE, Goldman, D, Weinberger, DR (2001). Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proceedings of the National Academy of Sciences USA 98, 6917–6922.CrossRefGoogle ScholarPubMed
Egan, MF, Kojima, M, Callicott, JH, Goldberg, TE, Kolachana, BS, Bertolino, A, Zaitsev, E, Gold, B, Goldman, D, Dean, M, Lu, B, Weinberger, DR (2003). The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 112, 257–269.Google Scholar
Ehlis, AC, Reif, A, Herrmann, MJ, Lesch, KP, Fallgatter, AJ (2007). Impact of catechol-O-methyltransferase on prefrontal brain functioning in schizophrenia spectrum disorders. Neuropsychopharmacology 32, 162–170.Google Scholar
Endicott, J, Spitzer, RL (1978). A diagnostic interview: the schedule for affective-disorders and schizophrenia. Archives of General Psychiatry 35, 837–844.CrossRefGoogle ScholarPubMed
Falls, DL (2003). Neuregulins: functions, forms, and signaling strategies. Experimental Cell Research 284, 14–30.Google Scholar
Fan, JB, Zhang, CS, Gu, NF, Li, XW, Sun, WW, Wang, HY, Feng, GY, St Clair, D, He, L (2005). Catechol-O-methyltransferase gene Val/Met functional polymorphism and risk of schizophrenia: a large-scale association study plus meta-analysis. Biological Psychiatry 57, 139–44.Google Scholar
First, M, Spitzer, R, Gibbon, M, Williams, J (1997). Structured Clinical Interview for DSM-IV Axis I Disorders. American Psychiatric Press: Washington, DC.Google Scholar
Franks, R, Adler, L, Waldo, M, Alpert, J, Freedman, R (1983). Neurophysiological studies of sensory gating in mania: comparison with schizophrenia. Biological Psychiatry 18, 989–1005.Google Scholar
Freedman, R, Adler, L, Myles-Worsley, M, Nagamoto, H, Miller, C, Kisley, M, McRae, K, Cawthra, E, Waldo, M (1996). Inhibitory gating of an evoked response to repeated auditory stimuli in schizophrenic and normal subjects. Archives of General Psychiatry 53, 1114–1121.CrossRefGoogle ScholarPubMed
Freedman, R, Adler, L, Waldo, M, Pachtman, E, Franks, R (1983). Neurophysiological evidence for a defect in inhibitory pathways in schizophrenia: comparison of medicated and drug-free patients. Biological Psychiatry 18, 537–551.Google ScholarPubMed
Freedman, R, Adler, LE, Gerhardt, GA, Waldo, M, Baker, N, Rose, GM, Drebing, C, Nagamoto, H, Bickfordwimer, P, Franks, R (1987). Neurobiological studies of sensory gating in schizophrenia. Schizophrenia Bulletin 13, 669–678.Google Scholar
Freedman, R, Coon, H, Myles-Worsley, M, Orr-Urtreger, A, Olincy, A, Davis, A, Polymeropoulos, M, Holik, J, Hopkins, J, Hoff, M, Rosenthal, J, Waldo, MC, Reimherr, F, Wender, P, Yaw, J, Young, D, Breese, CR, Adams, C, Patterson, D, Adler, LE, Kruglyak, L, Leonard, S, Byerley, W (1997). Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus. Proceedings of the National Academy of Sciences USA 94, 587–592.Google Scholar
Gail, MH, Pee, D, Carroll, R (2001). Effects of violations of assumptions on likelihood methods for estimating the penetrance of an autosomal dominant mutation from kin-cohort studies. Journal of Statistical Planning and Inference 96, 167–177.Google Scholar
Gallinat, J, Bajbouj, M, Sander, T, Schlattmann, P, Xu, K, Ferro, EF, Goldman, D, Winterer, G (2003). Association of the G1947A COMT (Val(108/158)Met) gene polymorphism with prefrontal P300 during information processing. Biological Psychiatry 54, 40–48.Google Scholar
Gauderman, WJ (2002). Sample size requirements for association studies of gene-gene interaction. American Journal of Epidemiology 155, 478–484.CrossRefGoogle ScholarPubMed
Georgieva, L, Dimitrova, A, Ivanov, D, Nikolov, I, Williams, NM, Grozeva, D, Zaharieva, I, Toncheva, D, Owen, MJ, Kirov, G, O'Donovan, MC (2008). Support for neuregulin 1 as a susceptibility gene for bipolar disorder and schizophrenia. Biological Psychiatry 64, 419–427.CrossRefGoogle Scholar
Glatt, SJ, Faraone, SV, Tsuang, MT (2003). Association between a functional catechol O-methyltransferase gene polymorphism and schizophrenia: meta-analysis of case-control and family-based studies. American Journal of Psychiatry 160, 469–476.CrossRefGoogle ScholarPubMed
Goghari, VM, Sponheim, SR (2008). Differential association of the COMT Val158Met polymorphism with clinical phenotypes in schizophrenia and bipolar disorder. Schizophrenia Research 103, 186–191.CrossRefGoogle ScholarPubMed
Golimbet, V, Gritsenko, I, Alfimova, M, Lebedeva, I, Lezheiko, T, Abramova, L, Kaleda, V, Ebstein, R (2006). Association study of COMT gene Val158Met polymorphism with auditory P300 and performance on neurocognitive tests in patients with schizophrenia and their relatives. World Journal of Biological Psychiatry 7, 238–245.CrossRefGoogle ScholarPubMed
Golimbet, VE, Lebedeva, IS, Korovaitseva, GI, Lezheiko, TV, Yumatova, PE (2008). Association of 5-HTTLPR serotonin transporter gene polymorphism and Val66Met brain-derived neurotrophic factor gene polymorphism with auditory N100 evoked potential amplitude in patients with endogenous psychoses. Bulletin of Experimental Biology and Medicine 146, 605–608.CrossRefGoogle ScholarPubMed
Gong, YG, Wu, CN, Xing, QH, Zhao, XZ, Zhu, J, He, L (2009). A two-method meta-analysis of Neuregulin 1(NRG1) association and heterogeneity in schizophrenia. Schizophrenia Research 111, 109–114.CrossRefGoogle ScholarPubMed
Gottesman, II, Gould, TD (2003). The endophenotype concept in psychiatry: etymology and strategic intentions. American Journal of Psychiatry 160, 636–645.Google Scholar
Gratacos, M, Gonzalez, JR, Mercader, JM, de Cid, R, Urretavizcaya, M, Estivill, X (2007). Brain-derived neurotrophic factor Val66Met and psychiatric disorders: meta-analysis of case-control studies confirm association to substance-related disorders, eating disorders, and schizophrenia. Biological Psychiatry 61, 911–922.Google Scholar
Green, EK, Raybould, R, Macgregor, S, Gordon-Smith, K, Heron, J, Hyde, S, Grozeva, D, Hamshere, M, Williams, N, Owen, MJ, O'Donovan, MC, Jones, L, Jones, I, Kirov, G, Craddock, N (2005). Operation of the schizophrenia susceptibility gene, neuregulin 1, across traditional diagnostic boundaries to increase risk for bipolar disorder. Archives of General Psychiatry 62, 642–668.CrossRefGoogle ScholarPubMed
Grunwald, T, Boutros, NN, Pezer, N, von Oertzen, J, Fernandez, G, Schaller, C, Elger, CE (2003). Neuronal substrates of sensory gating within the human brain. Biological Psychiatry 53, 511–519.Google Scholar
Hall, J, Whalley, HC, Job, DE, Baig, BJ, McIntosh, AM, Evans, KL, Thomson, PA, Porteous, DJ, Cunningham-Owens, DG, Johnstone, EC, Lawrie, SM (2006 a). A neuregulin 1 variant associated with abnormal cortical function and psychotic symptoms. Nature Neuroscience 9, 1477–1478.Google Scholar
Hall, MH, Schulze, K, Rijsdijk, F, Picchioni, M, Ettinger, U, Bramon, E, Freedman, R, Murray, RM, Sham, P (2006 b). Heritability and reliability of P300, P50 and duration mismatch negativity. Behavior Genetics 36, 845–857.Google Scholar
Hall, MH, Schulze, K, Sham, P, Kalidindi, S, McDonald, C, Bramon, E, Levy, DL, Murray, RM, Rijsdijk, F (2008). Further evidence for shared genetic effects between psychotic bipolar disorder and P50 suppression: a combined twin and family study. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 147B, 619–627.CrossRefGoogle ScholarPubMed
Han, DH, Park, DB, Choi, TY, Joo, SY, Lee, MK, Park, BR, Nishimura, R, Chu, CC, Renshaw, PF (2008). Effects of brain-derived neurotrophic factor-catecholamine-O-methyltransferase gene interaction on schizophrenic symptoms. Neuroreport 19, 1155–1158.CrossRefGoogle ScholarPubMed
Handoko, HY, Nyholt, DR, Hayward, NK, Nertney, DA, Hannah, DE, Windus, LC, McCormack, CM, Smith, HJ, Filippich, C, James, MR, Mowry, BJ (2005). Separate and interacting effects within the catechol-O-methyltransferase (COMT) are associated with schizophrenia. Molecular Psychiatry 10, 589–597.CrossRefGoogle ScholarPubMed
Hariri, AR, Goldberg, TE, Mattay, VS, Kolachana, BS, Callicott, JH, Egan, MF, Weinberger, DR (2003). Brain-derived neurotrophic factor val66met polymorphism affects human memory-related hippocampal activity and predicts memory performance. Journal of Neuroscience 23, 6690–6694.Google Scholar
Harrison, PJ, Weinberger, DR (2005). Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Molecular Psychiatry 10, 40–68; image 5.CrossRefGoogle ScholarPubMed
Hong, CJ, Yu, YW, Lin, CH, Tsai, SJ (2003). An association study of a brain-derived neurotrophic factor Val66Met polymorphism and clozapine response of schizophrenic patients. Neuroscience Letters 349, 206–208.Google Scholar
Ikeda, M, Takahashi, N, Saito, S, Aleksic, B, Watanabe, Y, Nunokawa, A, Yamanouchi, Y, Kitajima, T, Kinoshita, Y, Kishi, T, Kawashima, K, Hashimoto, R, Ujike, H, Inada, T, Someya, T, Takeda, M, Ozaki, N, Iwata, N (2008). Failure to replicate the association between NRG1 and schizophrenia using Japanese large sample. Schizophrenia Research 101, 1–8.CrossRefGoogle ScholarPubMed
Jonsson, EG, Edman-Ahlbom, B, Sillen, A, Gunnar, A, Kulle, B, Frigessi, A, Vares, M, Ekholm, B, Wode-Helgodt, B, Schumacher, J, Cichon, S, Agartz, I, Sedvall, GC, Hall, H, Terenius, L (2006). Brain-derived neurotrophic factor gene (BDNF) variants and schizophrenia: an association study. Progress in Neuropsychopharmacology and Biological Psychiatry 30, 924–933.Google Scholar
Jonsson, EG, Saetre, P, Vares, M, Andreou, D, Larsson, K, Timm, S, Rasmussen, HB, Djurovic, S, Melle, I, Andreassen, OA, Agartz, I, Werge, T, Hall, H, Terenius, L (2009). DTNBP1, NRG1, DAOA, DAO and GRM3 polymorphisms and schizophrenia: an association study. Neuropsychobiology 59, 142–150.Google Scholar
Judd, LL, McAdams, L, Budnick, B, Braff, DL (1992). Sensory gating deficits in schizophrenia: new results. American Journal of Psychiatry 149, 488–493.Google ScholarPubMed
Kanazawa, T, Glatt, SJ, Kia-Keating, B, Yoneda, H, Tsuang, MT (2007). Meta-analysis reveals no association of the Val66Met polymorphism of brain-derived neurotrophic factor with either schizophrenia or bipolar disorder. Psychiatric Genetics 17, 165–170.Google Scholar
Kawashima, K, Ikeda, M, Kishi, T, Kitajima, T, Yamanouchi, Y, Kinoshita, Y, Okochi, T, Aleksic, B, Tomita, M, Okada, T, Kunugi, H, Inada, T, Ozaki, N, Iwata, N (2009). BDNF is not associated with schizophrenia: data from a Japanese population study and meta-analysis. Schizophrenia Research 112, 72–79.Google Scholar
Kirov, G, Jones, I, McCandless, F, Craddock, N, Owen, MJ (1999). Family-based association studies of bipolar disorder with candidate genes involved in dopamine neurotransmission: DBH, DAT1, COMT, DRD2, DRD3 and DRD5. Molecular Psychiatry 4, 558–565.CrossRefGoogle ScholarPubMed
Kirov, G, Zaharieva, I, Georgieva, L, Moskvina, V, Nikolov, I, Cichon, S, Hillmer, A, Toncheva, D, Owen, MJ, O'Donovan, MC (2009). A genome-wide association study in 574 schizophrenia trios using DNA pooling. Molecular Psychiatry 14, 796–803.Google Scholar
Knight, RT, Staines, WR, Swick, D, Chao, LL (1999). Prefrontal cortex regulates inhibition and excitation in distributed neural networks. Acta Psychologica 101, 159–178.CrossRefGoogle ScholarPubMed
Lewis, CM, Levinson, DF, Wise, LH, DeLisi, LE, Straub, RE, Hovatta, I, Williams, NM, Schwab, SG, Pulver, AE, Faraone, SV, Brzustowicz, LM, Kaufmann, CA, Garver, DL, Gurling, HM, Lindholm, E, Coon, H, Moises, HW, Byerley, W, Shaw, SH, Mesen, A, Sherrington, R, O'Neill, FA, Walsh, D, Kendler, KS, Ekelund, J, Paunio, T, Lonnqvist, J, Peltonen, L, O'Donovan, MC, Owen, MJ, Wildenauer, DB, Maier, W, Nestadt, G, Blouin, JL, Antonarakis, SE, Mowry, BJ, Silverman, JM, Crowe, RR, Cloninger, CR, Tsuang, MT, Malaspina, D, Harkavy-Friedman, JM, Svrakic, DM, Bassett, AS, Holcomb, J, Kalsi, G, McQuillin, A, Brynjolfson, J, Sigmundsson, T, Petursson, H, Jazin, E, Zoëga, T, Helgason, T (2003). Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia. American Journal of Human Genetics 73, 34–48.Google Scholar
Li, D, Collier, DA, He, L (2006). Meta-analysis shows strong positive association of the neuregulin 1 (NRG1) gene with schizophrenia. Human Molecular Genetics 15, 1995–2002.Google Scholar
Li, T, Ball, D, Zhao, J, Murray, RM, Liu, X, Sham, PC, Collier, DA (2000). Family-based linkage disequilibrium mapping using SNP marker haplotypes: application to a potential locus for schizophrenia at chromosome 22q11. Molecular Psychiatry 5, 452.Google Scholar
Li, T, Sham, PC, Vallada, H, Xie, T, Tang, X, Murray, RM, Liu, X, Collier, DA (1996). Preferential transmission of the high activity allele of COMT in schizophrenia. Psychiatric Genetics 6, 131–133.Google Scholar
Light, GA, Malaspina, D, Geyer, MA, Luber, BM, Coleman, EA, Sackeim, HA, Braff, DL (1999). Amphetamine disrupts P50 suppression in normal subjects. Biological Psychiatry 46, 990–996.Google Scholar
Lohmueller, KE, Pearce, CL, Pike, M, Lander, ES, Hirschhorn, JN (2003). Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. Nature Genetics 33, 177–182.Google Scholar
Lohoff, FW, Sander, T, Ferraro, TN, Dahl, JP, Gallinat, J, Berrettini, WH (2005). Confirmation of association between the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene and bipolar I disorder. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 139B, 51–53.Google Scholar
Louchart-de la Chapelle, S, Nkam, I, Houy, E, Belmont, A, Menard, JF, Roussignol, AC, Siwek, O, Mezerai, M, Guillermou, M, Fouldrin, G, Levillain, D, Dollfus, S, Campion, D, Thibaut, F (2005). A concordance study of three electrophysiological measures in schizophrenia. American Journal of Psychiatry 162, 466–474.Google Scholar
Lu, BY, Martin, KE, Edgar, JC, Smith, AK, Lewis, SF, Escamilla, MA, Miller, GA, Canive, JM (2007). Effect of catechol O-methyltransferase val(158)met polymorphism on the p50 gating endophenotype in schizophrenia. Biological Psychiatry 62, 822–825.CrossRefGoogle ScholarPubMed
Maxwell, M (1992). Family Interview for Genetic Studies. Clinical Neurogenetics Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD.Google Scholar
Meyer-Lindenberg, A, Weinberger, DR (2006). Intermediate phenotypes and genetic mechanisms of psychiatric disorders. Nature Reviews. Neuroscience 7, 818–827.CrossRefGoogle ScholarPubMed
Munafo, MR, Attwood, AS, Flint, J (2008). Neuregulin 1 genotype and schizophrenia. Schizophrenia Bulletin 34, 9–12.CrossRefGoogle ScholarPubMed
Munafo, MR, Bowes, L, Clark, TG, Flint, J (2005). Lack of association of the COMT (Val158/108 Met) gene and schizophrenia: a meta-analysis of case-control studies. Molecular Psychiatry 10, 765–770.Google Scholar
Mynett-Johnson, LA, Murphy, VE, Claffey, E, Shields, DC, McKeon, P (1998). Preliminary evidence of an association between bipolar disorder in females and the catechol-O-methyltransferase gene. Psychiatric Genetics 8, 221–225.CrossRefGoogle ScholarPubMed
Nagamoto, HT, Adler, LE, Waldo, MC, Freedman, R (1989). Sensory gating in schizophrenics and normal controls: effects of changing stimulation interval. Biological Psychiatry 25, 549–561.Google Scholar
Neves-Pereira, M, Cheung, JK, Pasdar, A, Zhang, F, Breen, G, Yates, P, Sinclair, M, Crombie, C, Walker, N, St Clair, DM (2005). BDNF gene is a risk factor for schizophrenia in a Scottish population. Molecular Psychiatry 10, 208–212.CrossRefGoogle Scholar
Neves-Pereira, M, Mundo, E, Muglia, P, King, N, Macciardi, F, Kennedy, JL (2002). The brain-derived neurotrophic factor gene confers susceptibility to bipolar disorder: evidence from a family-based association study. American Journal of Human Genetics 71, 651–655.CrossRefGoogle ScholarPubMed
Norton, N, Williams, HJ, Owen, MJ (2006). An update on the genetics of schizophrenia. Current Opinion in Psychiatry 19, 158–164.Google Scholar
Numata, S, Ueno, S, Iga, J, Yamauchi, K, Hongwei, S, Ohta, K, Kinouchi, S, Shibuya-Tayoshi, S, Tayoshi, S, Aono, M, Kameoka, N, Sumitani, S, Tomotake, M, Kaneda, Y, Taniguchi, T, Ishimoto, Y, Ohmori, T (2006). Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism in schizophrenia is associated with age at onset and symptoms. Neuroscience Letters 401, 1–5.Google Scholar
Okochi, T, Ikeda, M, Kishi, T, Kawashima, K, Kinoshita, Y, Kitajima, T, Yamanouchi, Y, Tomita, M, Inada, T, Ozaki, N, Iwata, N (2009). Meta-analysis of association between genetic variants in COMT and schizophrenia: an update. Schizophrenia Research 110, 140–148.Google Scholar
Olincy, A, Martin, L (2005). Diminished suppression of the P50 auditory evoked potential in bipolar disorder subjects with a history of psychosis. American Journal of Psychiatry 162, 43–49.Google Scholar
Olincy, A, Ross, R, Harris, J, Young, D, McAndrews, M, Cawthra, E, McRae, K, Sullivan, B, Adler, L, Freedman, R (2000). The P50 auditory event-evoked potential in adult attention-deficit disorder: comparison with schizophrenia. Biological Psychiatry 47, 969–977.Google Scholar
Owen, MJ, Craddock, N, Jablensky, A (2007). The genetic deconstruction of psychosis. Schizophrenia Bulletin 33, 905–911.Google Scholar
Owen, MJ, Craddock, N, O'Donovan, MC (2005). Schizophrenia: genes at last? Trends in Genetics 21, 518–525.Google Scholar
Owen, MJ, Williams, NM, O'Donovan, MC (2004). The molecular genetics of schizophrenia: new findings promise new insights. Molecular Psychiatry 9, 14–27.Google Scholar
Pezawas, L, Verchinski, BA, Mattay, VS, Callicott, JH, Kolachana, BS, Straub, RE, Egan, MF, Meyer-Lindenberg, A, Weinberger, DR (2004). The brain-derived neurotrophic factor val66met polymorphism and variation in human cortical morphology. Journal of Neuroscience 24, 10099–10102.CrossRefGoogle ScholarPubMed
Poo, MM (2001). Neurotrophins as synaptic modulators. Nature Reviews. Neuroscience 2, 24–32.CrossRefGoogle ScholarPubMed
Prata, DP, Breen, G, Munro, J, Sinclair, M, Osborne, S, Li, T, Kerwin, R, St Clair, D, Collier, DA (2006). Bipolar 1 disorder is not associated with the RGS4, PRODH, COMT and GRK3 genes. Psychiatric Genetics 16, 229–230.CrossRefGoogle Scholar
Prata, DP, Breen, G, Osborne, S, Munro, J, St Clair, D, Collier, DA (2009). An association study of the neuregulin 1 gene, bipolar affective disorder and psychosis. Psychiatric Genetics 19, 113–116.CrossRefGoogle ScholarPubMed
Qian, L, Zhao, J, Shi, Y, Zhao, X, Feng, G, Xu, F, Zhu, S, He, L (2007). Brain-derived neurotrophic factor and risk of schizophrenia: an association study and meta-analysis. Biochemical and Biophysical Research Communications 353, 738–743.Google Scholar
Riley, B, Kendler, KS (2006). Molecular genetic studies of schizophrenia. European Journal of Human Genetics 14, 669–680.Google Scholar
Rosa, A, Cuesta, MJ, Fatjo-Vilas, M, Peralta, V, Zarzuela, A, Fananas, L (2006). The Val66Met polymorphism of the brain-derived neurotrophic factor gene is associated with risk for psychosis: evidence from a family-based association study. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 141B, 135–138.Google Scholar
Sanchez-Morla, EM, Garcia-Jimenez, MA, Barabash, A, Martinez-Vizcaino, V, Mena, J, Cabranes-Diaz, JA, Baca-Baldomero, E, Santos, JL (2008). P50 sensory gating deficit is a common marker of vulnerability to bipolar disorder and schizophrenia. Acta Psychiatrica Scandinavica 117, 313–318.Google Scholar
Sand, PG, Eichhammer, P, Langguth, B, Hajak, G (2006). COMT association data in schizophrenia: new caveats. Biological Psychiatry 60, 663–664; author reply 664–665.Google Scholar
Sanders, AR, Duan, J, Levinson, DF, Shi, J, He, D, Hou, C, Burrell, GJ, Rice, JP, Nertney, DA, Olincy, A, Rozic, P, Vinogradov, S, Buccola, NG, Mowry, BJ, Freedman, R, Amin, F, Black, DW, Silverman, JM, Byerley, WF, Crowe, RR, Cloninger, CR, Martinez, M, Gejman, PV (2008). No significant association of 14 candidate genes with schizophrenia in a large European ancestry sample: implications for psychiatric genetics. American Journal of Psychiatry 165, 497–506.Google Scholar
Schulze, KK, Hall, MH, McDonald, C, Marshall, N, Walshe, M, Murray, RM, Bramon, E (2007). P50 auditory evoked potential suppression in bipolar disorder patients with psychotic features and their unaffected relatives. Biological Psychiatry 62, 121–128.Google Scholar
Serretti, A, Cusin, C, Cristina, S, Lorenzi, C, Lilli, R, Lattuada, E, Grieco, G, Costa, A, Santorelli, F, Barale, F, Smeraldi, E, Nappi, G (2003). Multicentre Italian family-based association study on tyrosine hydroxylase, catechol-O-methyl transferase and Wolfram syndrome 1 polymorphisms in mood disorders. Psychiatric Genetics 13, 121–126.Google Scholar
Shifman, S, Bronstein, M, Sternfeld, M, Pisanté, A, Weizman, A, Reznik, I, Spivak, B, Grisaru, N, Karp, L, Schiffer, R, Kotler, M, Strous, RD, Swartz-Vanetik, M, Knobler, HY, Shinar, E, Yakir, B, Zak, NB, Darvasi, A (2004). COMT: a common susceptibility gene in bipolar disorder and schizophrenia. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 128B, 61–64.Google Scholar
Shifman, S, Bronstein, M, Sternfeld, M, Pisanté-Shalom, A, Lev-Lehman, E, Weizman, A, Reznik, I, Spivak, B, Grisaru, N, Karp, L, Schiffer, R, Kotler, M, Strous, RD, Swartz-Vanetik, M, Knobler, HY, Shinar, E, Beckmann, JS, Yakir, B, Risch, N, Zak, NB, Darvasi, A (2002). A highly significant association between a COMT haplotype and schizophrenia. American Journal of Human Genetics 71, 1296–1302.Google Scholar
Siegel, C, Waldo, M, Mizner, G, Adler, L, Freedman, R (1984). Deficits in sensory gating in schizophrenic patients and their relatives. Archives of General Psychiatry 41, 607–612.Google Scholar
Sklar, P, Gabriel, SB, McInnis, MG, Bennett, P, Lim, YM, Tsan, G, Schaffner, S, Kirov, G, Jones, I, Owen, M, Craddock, N, DePaulo, JR, Lander, ES (2002). Family-based association study of 76 candidate genes in bipolar disorder: BDNF is a potential risk locus. Brain-derived neutrophic factor. Molecular Psychiatry 7, 579–593.Google Scholar
Sklar, P, Smoller, JW, Fan, J, Ferreira, MA, Perlis, RH, Chambert, K, Nimgaonkar, VL, McQueen, MB, Faraone, SV, Kirby, A, de Bakker, PI, Ogdie, MN, Thase, ME, Sachs, GS, Todd-Brown, K, Gabriel, SB, Sougnez, C, Gates, C, Blumenstiel, B, Defelice, M, Ardlie, KG, Franklin, J, Muir, WJ, McGhee, KA, MacIntyre, DJ, McLean, A, VanBeck, M, McQuillin, A, Bass, NJ, Robinson, M, Lawrence, J, Anjorin, A, Curtis, D, Scolnick, EM, Daly, MJ, Blackwood, DH, Gurling, HM, Purcell, SM (2008). Whole-genome association study of bipolar disorder. Molecular Psychiatry 13, 558–569.Google Scholar
Smith, DA, Boutros, NN, Schwarzkopf, SB (1994). Reliability of P50 auditory event-related potential indexes of sensory gating. Psychophysiology 31, 495–502.Google Scholar
Stefansson, H, Sarginson, J, Kong, A, Yates, P, Steinthorsdottir, V, Gudfinnsson, E, Gunnarsdottir, S, Walker, N, Petursson, H, Crombie, C, Ingason, A, Gulcher, JR, Stefansson, K, St Clair, D (2003). Association of neuregulin 1 with schizophrenia confirmed in a Scottish population. American Journal of Human Genetics 72, 83–87.Google Scholar
Stefansson, H, Sigurdsson, E, Steinthorsdottir, V, Bjornsdottir, S, Sigmundsson, T, Ghosh, S, Brynjolfsson, J, Gunnarsdottir, S, Ivarsson, O, Chou, TT, Hjaltason, O, Birgisdottir, B, Jonsson, H, Gudnadottir, VG, Gudmundsdottir, E, Bjornsson, A, Ingvarsson, B, Ingason, A, Sigfusson, S, Hardardottir, H, Harvey, RP, Lai, D, Zhou, M, Brunner, D, Mutel, V, Gonzalo, A, Lemke, G, Sainz, J, Johannesson, G, Andresson, T, Gudbjartsson, D, Manolescu, A, Frigge, ML, Gurney, ME, Kong, A, Gulcher, JR, Petursson, H, Stefansson, K (2002). Neuregulin 1 and susceptibility to schizophrenia. American Journal of Human Genetics 71, 877–892.Google Scholar
Stefansson, H, Steinthorsdottir, V, Thorgeirsson, TE, Gulcher, JR, Stefansson, K (2004). Neuregulin 1 and schizophrenia. Annals of Medicine 36, 62–71.Google Scholar
Stevens, KE, Freedman, R, Collins, AC, Hall, M, Leonard, S, Marks, MJ, Rose, GM (1996). Genetic correlation of inhibitory gating of hippocampal auditory evoked response and alpha-bungarotoxin-binding nicotinic cholinergic receptors in inbred mouse strains. Neuropsychopharmacology 15, 152–162.Google Scholar
Szeszko, PR, Lipsky, R, Mentschel, C, Robinson, D, Gunduz-Bruce, H, Sevy, S, Ashtari, M, Napolitano, B, Bilder, RM, Kane, JM, Goldman, D, Malhotra, AK (2005). Brain-derived neurotrophic factor val66met polymorphism and volume of the hippocampal formation. Molecular Psychiatry 10, 631–636.Google Scholar
Takahashi, M, Shirakawa, O, Toyooka, K, Kitamura, N, Hashimoto, T, Maeda, K, Koizumi, S, Wakabayashi, K, Takahashi, H, Someya, T, Nawa, H (2000). Abnormal expression of brain-derived neurotrophic factor and its receptor in the corticolimbic system of schizophrenic patients. Molecular Psychiatry 5, 293–300.Google Scholar
Tosato, S, Dazzan, P, Collier, D (2005). Association between the neuregulin 1 gene and schizophrenia: a systematic review. Schizophrenia Bulletin 31, 613–617.CrossRefGoogle ScholarPubMed
Tsai, SJ, Yu, YWY, Chen, TJ, Chen, JY, Liou, YJ, Chen, MC, Hong, CJ (2003). Association study of a functional catechol-O-methyltransferase gene polymorphism and cognitive function in healthy females. Neuroscience Letters 338, 123–126.Google Scholar
Venables, P (1964). Input dysfunction in schizophrenia. In Progress in Experimental Personality Research ( ed. Maher, B. A.), pp. 1–47. Academic Press: New York.Google Scholar
Waldo, M, Cawthra, E, Adler, L, Dubester, S, Staunton, M, Nagamoto, H, Baker, N, Madison, A, Simon, J, Scherzinger, A, Drebing, C, Gerhardt, G, Freedman, R (1994). Auditory sensory gating, hippocampal volume, and catecholamine metabolism in schizophrenics and their siblings. Schizophrenia Research 12, 93–106.Google Scholar
Waldo, M, Myles-Worsley, M, Madison, A, Byerley, W, Freedman, R (1995). Sensory gating deficits in parents of schizophrenics. American Journal of Medical Genetics 60, 506–511.CrossRefGoogle ScholarPubMed
Waldo, MC, Adler, LE, Freedman, R (1988). Defects in auditory sensory gating and their apparent compensation in relatives of schizophrenics. Schizophrenia Research 1, 19–24.Google Scholar
Waldo, MC, Adler, LE, Leonard, S, Olincy, A, Ross, RG, Harris, JG, Freedman, R (2000). Familial transmission of risk factors in the first-degree relatives of schizophrenic people. Biological Psychiatry 47, 231–239.Google Scholar
Waldo, MC, Carey, G, Myles-Worsley, M, Cawthra, E, Adler, LE, Nagamato, HT, Wender, P, Byerley, W, Plaetke, R, Freedman, R (1991). Codistribution of a sensory gating deficit and schizophrenia in multi-affected families. Psychiatry Research 39, 257–284.Google Scholar
Ward, PB, Hoffer, LD, Leibert, B, Catts, SV, O'Donnell, M, Adler, LE (1996). Replication of a P50 auditory gating deficit in Australian patients with schizophrenia. Psychiatry Research 64, 121–135.Google Scholar
Weickert, CS, Hyde, TM, Lipska, BK, Herman, MM, Weinberger, DR, Kleinman, JE (2003). Reduced brain-derived neurotrophic factor in prefrontal cortex of patients with schizophrenia. Molecular Psychiatry 8, 592–610.Google Scholar
Williams, NM, Preece, A, Spurlock, G, Norton, N, Williams, HJ, Zammit, S, O'Donovan, MC, Owen, MJ (2003). Support for genetic variation in neuregulin 1 and susceptibility to schizophrenia. Molecular Psychiatry 8, 485–487.Google Scholar
Winterer, G, Weinberger, DR (2004). Genes, dopamine and cortical signal-to-noise ratio in schizophrenia. Trends in Neuroscience 27, 683–690.Google Scholar
Xu, MQ, St Clair, D, Ott, J, Feng, GY, He, L (2007). Brain-derived neurotrophic factor gene C-270T and Val66Met functional polymorphisms and risk of schizophrenia: a moderate-scale population-based study and meta-analysis. Schizophrenia Research 91, 6–13.Google Scholar
Yamada, K, Nabeshima, T (2003). Brain-derived neurotrophic factor/TrkB signaling in memory processes. Journal of Pharmacological Sciences 91, 267–270.Google Scholar
Young, D, Waldo, M, Rutledge, JH, Freedman, R (1996). Heritability of inhibitory gating of the P50 auditory-evoked potential in monozygotic and dizygotic twins. Biological Psychiatry 33, 113–117.Google ScholarPubMed
Yue, C, Wu, T, Deng, W, Wang, G, Sun, X (2009). Comparison of visual evoked-related potentials in healthy young adults of different catechol-O-methyltransferase genotypes in a continuous 3-back task. Neuroreport 20, 521–524.Google Scholar
Zhang, Z, Lindpaintner, K, Che, R, He, Z, Wang, P, Yang, P, Feng, G, He, L, Shi, Y (2009). The Val/Met functional polymorphism in COMT confers susceptibility to bipolar disorder: evidence from an association study and a meta-analysis. Journal of Neural Transmission 116, 1193–1200.Google Scholar
Zintzaras, E (2007). Brain-derived neurotrophic factor gene polymorphisms and schizophrenia: a meta-analysis. Psychiatric Genetics 17, 69–75.CrossRefGoogle ScholarPubMed