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Erschienen in: European Archives of Psychiatry and Clinical Neuroscience 4/2014

01.06.2014 | Original Paper

Association of variants in DRD2 and GRM3 with motor and cognitive function in first-episode psychosis

verfasst von: Rebekka Lencer, Jeffrey R. Bishop, Margret S. H. Harris, James L. Reilly, Shitalben Patel, Rick Kittles, Konasale M. Prasad, Vishwajit L. Nimgaonkar, Matcheri S. Keshavan, John A. Sweeney

Erschienen in: European Archives of Psychiatry and Clinical Neuroscience | Ausgabe 4/2014

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Abstract

Similar smooth pursuit eye tracking dysfunctions are present across psychotic disorders. They include pursuit initiation and maintenance deficits that implicate different functional brain systems. This candidate gene study examined psychosis-related genotypes regulating dopamine and glutamate neurotransmission in relation to these pursuit deficits. One hundred and thirty-eight untreated first-episode patients with a psychotic disorder were genotyped for four markers in DRD2 and four markers in GRM3. The magnitude of eye movement abnormality in patients was defined in relation to performance of matched healthy controls (N = 130). Eighty three patients were followed after 6 weeks of antipsychotic treatment. At baseline, patients with a −141C deletion in DRD2 rs1799732 had slower initiation eye velocity and longer pursuit latency than CC insertion carriers. Further, GRM3 rs274622_CC carriers had poorer pursuit maintenance than T-carriers. Antipsychotic treatment resulted in prolonged pursuit latency in DRD2 rs1799732_CC insertion carriers and a decline in pursuit maintenance in GRM3 rs6465084_GG carriers. The present study demonstrates for the first time that neurophysiological measures of motor and neurocognitive deficits in patients with psychotic disorders have different associations with genes regulating dopamine and glutamate systems, respectively. Alterations in striatal D2 receptor activity through the −141C Ins/Del polymorphism could contribute to pursuit initiation deficits in psychotic disorders. Alterations in GRM3 coding for the mGluR3 protein may impair pursuit maintenance by compromising higher perceptual and cognitive processes that depend on optimal glutamate signaling in corticocortical circuits. DRD2 and GRM3 genotypes also selectively modulated the severity of adverse motor and neurocognitive changes resulting from antipsychotic treatment.
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Literatur
1.
Zurück zum Zitat Gottesman II, Gould TD (2003) The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 160(4):636–645PubMedCrossRef Gottesman II, Gould TD (2003) The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 160(4):636–645PubMedCrossRef
2.
Zurück zum Zitat Javitt DC, Spencer KM, Thaker GK, Winterer G, Hajos M (2008) Neurophysiological biomarkers for drug development in schizophrenia. Nat Rev 7(1):68–83 Javitt DC, Spencer KM, Thaker GK, Winterer G, Hajos M (2008) Neurophysiological biomarkers for drug development in schizophrenia. Nat Rev 7(1):68–83
3.
Zurück zum Zitat Holzman PS (1992) Behavioral markers of schizophrenia useful for genetic studies. J Psychiatr Res 26(4):427–445PubMedCrossRef Holzman PS (1992) Behavioral markers of schizophrenia useful for genetic studies. J Psychiatr Res 26(4):427–445PubMedCrossRef
5.
Zurück zum Zitat Lencer R, Malchow CP, Krecker K, Nolte A, Pinnow M, von Siefart SZ, Schwinger E, Arolt V (1999) Smooth pursuit performance in families with multiple occurrence of schizophrenia and nonpsychotic families. Biol Psychiatry 45(6):694–703PubMedCrossRef Lencer R, Malchow CP, Krecker K, Nolte A, Pinnow M, von Siefart SZ, Schwinger E, Arolt V (1999) Smooth pursuit performance in families with multiple occurrence of schizophrenia and nonpsychotic families. Biol Psychiatry 45(6):694–703PubMedCrossRef
6.
Zurück zum Zitat Levy DL, Sereno AB, Gooding DC, O’Driscoll GA (2010) Eye tracking dysfunction in schizophrenia: characterization and pathophysiology. Curr Top Behav Neurosci 4:311–347PubMedCentralPubMedCrossRef Levy DL, Sereno AB, Gooding DC, O’Driscoll GA (2010) Eye tracking dysfunction in schizophrenia: characterization and pathophysiology. Curr Top Behav Neurosci 4:311–347PubMedCentralPubMedCrossRef
7.
Zurück zum Zitat Sweeney JA, Clementz BA, Haas GL, Escobar MD, Drake K, Frances AJ (1994) Eye tracking dysfunction in schizophrenia: characterization of component eye movement abnormalities, diagnostic specificity, and the role of attention. J Abnorm Psychol 103(2):222–230PubMedCrossRef Sweeney JA, Clementz BA, Haas GL, Escobar MD, Drake K, Frances AJ (1994) Eye tracking dysfunction in schizophrenia: characterization of component eye movement abnormalities, diagnostic specificity, and the role of attention. J Abnorm Psychol 103(2):222–230PubMedCrossRef
8.
Zurück zum Zitat Calkins ME, Iacono WG, Ones DS (2008) Eye movement dysfunction in first-degree relatives of patients with schizophrenia: a meta-analytic evaluation of candidate endophenotypes. Brain Cogn 68(3):436–461PubMedCrossRef Calkins ME, Iacono WG, Ones DS (2008) Eye movement dysfunction in first-degree relatives of patients with schizophrenia: a meta-analytic evaluation of candidate endophenotypes. Brain Cogn 68(3):436–461PubMedCrossRef
9.
Zurück zum Zitat 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, Zoega T, Helgason T (2003) Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia. Am J Hum Genet 73(1):34–48. doi:10.1086/376549 PubMedCentralPubMedCrossRef 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, Zoega T, Helgason T (2003) Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia. Am J Hum Genet 73(1):34–48. doi:10.​1086/​376549 PubMedCentralPubMedCrossRef
10.
Zurück zum Zitat Lichtenstein P, Yip BH, Bjork C, Pawitan Y, Cannon TD, Sullivan PF, Hultman CM (2009) Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet 373(9659):234–239PubMedCrossRef Lichtenstein P, Yip BH, Bjork C, Pawitan Y, Cannon TD, Sullivan PF, Hultman CM (2009) Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet 373(9659):234–239PubMedCrossRef
11.
Zurück zum Zitat Williams HJ, Craddock N, Russo G, Hamshere ML, Moskvina V, Dwyer S, Smith RL, Green E, Grozeva D, Holmans P, Owen MJ, O’Donovan MC (2011) Most genome-wide significant susceptibility loci for schizophrenia and bipolar disorder reported to date cross-traditional diagnostic boundaries. Hum Mol Genet 20(2):387–391. doi:10.1093/hmg/ddq471 PubMedCentralPubMedCrossRef Williams HJ, Craddock N, Russo G, Hamshere ML, Moskvina V, Dwyer S, Smith RL, Green E, Grozeva D, Holmans P, Owen MJ, O’Donovan MC (2011) Most genome-wide significant susceptibility loci for schizophrenia and bipolar disorder reported to date cross-traditional diagnostic boundaries. Hum Mol Genet 20(2):387–391. doi:10.​1093/​hmg/​ddq471 PubMedCentralPubMedCrossRef
12.
Zurück zum Zitat McIntosh AM, Moorhead TW, McKirdy J, Hall J, Sussmann JE, Stanfield AC, Harris JM, Johnstone EC, Lawrie SM (2009) Prefrontal gyral folding and its cognitive correlates in bipolar disorder and schizophrenia. Acta Psychiatr Scand 119(3):192–198PubMedCrossRef McIntosh AM, Moorhead TW, McKirdy J, Hall J, Sussmann JE, Stanfield AC, Harris JM, Johnstone EC, Lawrie SM (2009) Prefrontal gyral folding and its cognitive correlates in bipolar disorder and schizophrenia. Acta Psychiatr Scand 119(3):192–198PubMedCrossRef
13.
Zurück zum Zitat McIntosh AM, Whalley HC, McKirdy J, Hall J, Sussmann JE, Shankar P, Johnstone EC, Lawrie SM (2008) Prefrontal function and activation in bipolar disorder and schizophrenia. Am J Psychiatry 165(3):378–384PubMedCrossRef McIntosh AM, Whalley HC, McKirdy J, Hall J, Sussmann JE, Shankar P, Johnstone EC, Lawrie SM (2008) Prefrontal function and activation in bipolar disorder and schizophrenia. Am J Psychiatry 165(3):378–384PubMedCrossRef
14.
Zurück zum Zitat Lencer R, Reilly JL, Harris MS, Sprenger A, Keshavan MS, Sweeney JA (2010) Sensorimotor transformation deficits for smooth pursuit in first-episode affective psychoses and schizophrenia. Biol Psychiatry 67(3):217–223PubMedCentralPubMedCrossRef Lencer R, Reilly JL, Harris MS, Sprenger A, Keshavan MS, Sweeney JA (2010) Sensorimotor transformation deficits for smooth pursuit in first-episode affective psychoses and schizophrenia. Biol Psychiatry 67(3):217–223PubMedCentralPubMedCrossRef
15.
Zurück zum Zitat Lencer R, Trillenberg P, Trillenberg-Krecker K, Junghanns K, Kordon A, Broocks A, Hohagen F, Heide W, Arolt V (2004) Smooth pursuit deficits in schizophrenia, affective disorder and obsessive-compulsive disorder. Psychol Med 34(3):451–460PubMedCrossRef Lencer R, Trillenberg P, Trillenberg-Krecker K, Junghanns K, Kordon A, Broocks A, Hohagen F, Heide W, Arolt V (2004) Smooth pursuit deficits in schizophrenia, affective disorder and obsessive-compulsive disorder. Psychol Med 34(3):451–460PubMedCrossRef
16.
Zurück zum Zitat Sweeney JA, Luna B, Haas GL, Keshavan MS, Mann JJ, Thase ME (1999) Pursuit tracking impairments in schizophrenia and mood disorders: step-ramp studies with unmedicated patients. Biol Psychiatry 46(5):671–680PubMedCrossRef Sweeney JA, Luna B, Haas GL, Keshavan MS, Mann JJ, Thase ME (1999) Pursuit tracking impairments in schizophrenia and mood disorders: step-ramp studies with unmedicated patients. Biol Psychiatry 46(5):671–680PubMedCrossRef
17.
Zurück zum Zitat Blackwood DH, Sharp CW, Walker MT, Doody GA, Glabus MF, Muir WJ (1996) Implications of comorbidity for genetic studies of bipolar disorder: P300 and eye tracking as biological markers for illness. Br J Psychiatry Suppl 30:85–92PubMed Blackwood DH, Sharp CW, Walker MT, Doody GA, Glabus MF, Muir WJ (1996) Implications of comorbidity for genetic studies of bipolar disorder: P300 and eye tracking as biological markers for illness. Br J Psychiatry Suppl 30:85–92PubMed
18.
Zurück zum Zitat Kathmann N, Hochrein A, Uwer R, Bondy B (2003) Deficits in gain of smooth pursuit eye movements in schizophrenia and affective disorder patients and their unaffected relatives. Am J Psychiatry 160(4):696–702PubMedCrossRef Kathmann N, Hochrein A, Uwer R, Bondy B (2003) Deficits in gain of smooth pursuit eye movements in schizophrenia and affective disorder patients and their unaffected relatives. Am J Psychiatry 160(4):696–702PubMedCrossRef
19.
Zurück zum Zitat Lencer R, Sprenger A, Harris MS, Reilly JL, Keshavan MS, Sweeney JA (2008) Effects of second-generation antipsychotic medication on smooth pursuit performance in antipsychotic-naive schizophrenia. Arch Gen Psychiatry 65(10):1146–1154PubMedCentralPubMedCrossRef Lencer R, Sprenger A, Harris MS, Reilly JL, Keshavan MS, Sweeney JA (2008) Effects of second-generation antipsychotic medication on smooth pursuit performance in antipsychotic-naive schizophrenia. Arch Gen Psychiatry 65(10):1146–1154PubMedCentralPubMedCrossRef
20.
Zurück zum Zitat Hutton SB, Crawford TJ, Gibbins H, Cuthbert I, Barnes TR, Kennard C, Joyce EM (2001) Short and long term effects of antipsychotic medication on smooth pursuit eye tracking in schizophrenia. Psychopharmacology 157(3):284–291PubMedCrossRef Hutton SB, Crawford TJ, Gibbins H, Cuthbert I, Barnes TR, Kennard C, Joyce EM (2001) Short and long term effects of antipsychotic medication on smooth pursuit eye tracking in schizophrenia. Psychopharmacology 157(3):284–291PubMedCrossRef
21.
Zurück zum Zitat Sweeney JA, Haas GL, Li S, Weiden PJ (1994) Selective effects of antipsychotic medications on eye-tracking performance in schizophrenia. Psychiatry Res 54(2):185–198PubMedCrossRef Sweeney JA, Haas GL, Li S, Weiden PJ (1994) Selective effects of antipsychotic medications on eye-tracking performance in schizophrenia. Psychiatry Res 54(2):185–198PubMedCrossRef
22.
Zurück zum Zitat Sweeney JA, Luna B, Srinivasagam NM, Keshavan MS, Schooler NR, Haas GL, Carl JR (1998) Eye tracking abnormalities in schizophrenia: evidence for dysfunction in the frontal eye fields. Biol Psychiatry 44(8):698–708PubMedCrossRef Sweeney JA, Luna B, Srinivasagam NM, Keshavan MS, Schooler NR, Haas GL, Carl JR (1998) Eye tracking abnormalities in schizophrenia: evidence for dysfunction in the frontal eye fields. Biol Psychiatry 44(8):698–708PubMedCrossRef
23.
Zurück zum Zitat Lencer R, Trillenberg P (2008) Neurophysiology and neuroanatomy of smooth pursuit in humans. Brain Cogn 68(3):219–228PubMedCrossRef Lencer R, Trillenberg P (2008) Neurophysiology and neuroanatomy of smooth pursuit in humans. Brain Cogn 68(3):219–228PubMedCrossRef
24.
Zurück zum Zitat Helmchen C, Pohlmann J, Trillenberg P, Lencer R, Graf J, Sprenger A (2012) Role of anticipation and prediction in smooth pursuit eye movement control in Parkinson’s disease. Mov Disord 27(8):1012–1018. doi:10.1002/mds.25042 PubMedCrossRef Helmchen C, Pohlmann J, Trillenberg P, Lencer R, Graf J, Sprenger A (2012) Role of anticipation and prediction in smooth pursuit eye movement control in Parkinson’s disease. Mov Disord 27(8):1012–1018. doi:10.​1002/​mds.​25042 PubMedCrossRef
25.
Zurück zum Zitat Lencer R, Nagel M, Sprenger A, Zapf S, Erdmann C, Heide W, Binkofski F (2004) Cortical mechanisms of smooth pursuit eye movements with target blanking. An fMRI study. Eur J Neurosci 19(5):1430–1436PubMedCrossRef Lencer R, Nagel M, Sprenger A, Zapf S, Erdmann C, Heide W, Binkofski F (2004) Cortical mechanisms of smooth pursuit eye movements with target blanking. An fMRI study. Eur J Neurosci 19(5):1430–1436PubMedCrossRef
26.
Zurück zum Zitat Burke MR, Barnes GR (2008) Brain and behavior: a task-dependent eye movement study. Cereb Cortex 18(1):126–135PubMedCrossRef Burke MR, Barnes GR (2008) Brain and behavior: a task-dependent eye movement study. Cereb Cortex 18(1):126–135PubMedCrossRef
29.
Zurück zum Zitat Vorstman JA, Turetsky BI, Sijmens-Morcus ME, de Sain MG, Dorland B, Sprong M, Rappaport EF, Beemer FA, Emanuel BS, Kahn RS, van Engeland H, Kemner C (2009) Proline affects brain function in 22q11DS children with the low activity COMT 158 allele. Neuropsychopharmacology 34(3):739–746. doi:10.1038/npp.2008.132 PubMedCentralPubMedCrossRef Vorstman JA, Turetsky BI, Sijmens-Morcus ME, de Sain MG, Dorland B, Sprong M, Rappaport EF, Beemer FA, Emanuel BS, Kahn RS, van Engeland H, Kemner C (2009) Proline affects brain function in 22q11DS children with the low activity COMT 158 allele. Neuropsychopharmacology 34(3):739–746. doi:10.​1038/​npp.​2008.​132 PubMedCentralPubMedCrossRef
30.
Zurück zum Zitat Park BL, Shin HD, Cheong HS, Park CS, Sohn JW, Kim BJ, Seo HK, Kim JW, Kim KH, Shin TM, Choi IG, Kim SG, Woo SI (2009) Association analysis of COMT polymorphisms with schizophrenia and smooth pursuit eye movement abnormality. J Hum Genet 54(12):709–712. doi:10.1038/jhg.2009.102 PubMedCrossRef Park BL, Shin HD, Cheong HS, Park CS, Sohn JW, Kim BJ, Seo HK, Kim JW, Kim KH, Shin TM, Choi IG, Kim SG, Woo SI (2009) Association analysis of COMT polymorphisms with schizophrenia and smooth pursuit eye movement abnormality. J Hum Genet 54(12):709–712. doi:10.​1038/​jhg.​2009.​102 PubMedCrossRef
31.
Zurück zum Zitat Rybakowski JK, Borkowska A, Czerski PM, Hauser J (2001) Dopamine D3 receptor (DRD3) gene polymorphism is associated with the intensity of eye movement disturbances in schizophrenic patients and healthy subjects. Mol Psychiatry 6(6):718–724PubMedCrossRef Rybakowski JK, Borkowska A, Czerski PM, Hauser J (2001) Dopamine D3 receptor (DRD3) gene polymorphism is associated with the intensity of eye movement disturbances in schizophrenic patients and healthy subjects. Mol Psychiatry 6(6):718–724PubMedCrossRef
32.
Zurück zum Zitat Rybakowski JK, Borkowska A, Czerski PM, Hauser J (2002) Eye movement disturbances in schizophrenia and a polymorphism of catechol-O-methyltransferase gene. Psychiatry Res 113(1–2):49–57PubMedCrossRef Rybakowski JK, Borkowska A, Czerski PM, Hauser J (2002) Eye movement disturbances in schizophrenia and a polymorphism of catechol-O-methyltransferase gene. Psychiatry Res 113(1–2):49–57PubMedCrossRef
33.
Zurück zum Zitat Thaker GK, Wonodi I, Avila MT, Hong LE, Stine OC (2004) Catechol O-methyltransferase polymorphism and eye tracking in schizophrenia: a preliminary report. Am J Psychiatry 161(12):2320–2322PubMedCrossRef Thaker GK, Wonodi I, Avila MT, Hong LE, Stine OC (2004) Catechol O-methyltransferase polymorphism and eye tracking in schizophrenia: a preliminary report. Am J Psychiatry 161(12):2320–2322PubMedCrossRef
34.
Zurück zum Zitat Wonodi I, Hong LE, Stine OC, Mitchell BD, Elliott A, Roberts RC, Conley RR, McMahon RP, Thaker GK (2009) Dopamine transporter polymorphism modulates oculomotor function and DAT1 mRNA expression in schizophrenia. Am J Med Genet B Neuropsychiatr Genet 150B(2):282–289PubMedCentralPubMedCrossRef Wonodi I, Hong LE, Stine OC, Mitchell BD, Elliott A, Roberts RC, Conley RR, McMahon RP, Thaker GK (2009) Dopamine transporter polymorphism modulates oculomotor function and DAT1 mRNA expression in schizophrenia. Am J Med Genet B Neuropsychiatr Genet 150B(2):282–289PubMedCentralPubMedCrossRef
35.
Zurück zum Zitat Haraldsson HM, Ettinger U, Magnusdottir BB, Ingason A, Hutton SB, Sigmundsson T, Sigurdsson E, Petursson H (2010) Neuregulin-1 genotypes and eye movements in schizophrenia. Eur Arch Psychiatry Clin Neurosci 260(1):77–85. doi:10.1007/s00406-009-0032-2 PubMedCrossRef Haraldsson HM, Ettinger U, Magnusdottir BB, Ingason A, Hutton SB, Sigmundsson T, Sigurdsson E, Petursson H (2010) Neuregulin-1 genotypes and eye movements in schizophrenia. Eur Arch Psychiatry Clin Neurosci 260(1):77–85. doi:10.​1007/​s00406-009-0032-2 PubMedCrossRef
36.
Zurück zum Zitat Pasaje CF, Bae JS, Park BL, Cheong HS, Kim JH, Park TJ, Lee JS, Kim Y, Park CS, Kim BJ, Cha B, Kim JW, Choi WH, Shin TM, Choi IG, Hwang J, Shin HD, Woo SI (2011) Neuregulin 3 does not confer risk for schizophrenia and smooth pursuit eye movement abnormality in a Korean population. Genes, brain, behav 10(8):828–833. doi:10.1111/j.1601-183X.2011.00722.x CrossRef Pasaje CF, Bae JS, Park BL, Cheong HS, Kim JH, Park TJ, Lee JS, Kim Y, Park CS, Kim BJ, Cha B, Kim JW, Choi WH, Shin TM, Choi IG, Hwang J, Shin HD, Woo SI (2011) Neuregulin 3 does not confer risk for schizophrenia and smooth pursuit eye movement abnormality in a Korean population. Genes, brain, behav 10(8):828–833. doi:10.​1111/​j.​1601-183X.​2011.​00722.​x CrossRef
37.
Zurück zum Zitat Cheong HS, Park BL, Kim EM, Park CS, Sohn JW, Kim BJ, Kim JW, Kim KH, Shin TM, Choi IG, Han SW, Hwang J, Koh I, Shin HD, Woo SI (2011) Association of RANBP1 haplotype with smooth pursuit eye movement abnormality. Am J Med Genet B Neuropsychiatr Genet 156B(1):67–71. doi:10.1002/ajmg.b.31139 PubMedCrossRef Cheong HS, Park BL, Kim EM, Park CS, Sohn JW, Kim BJ, Kim JW, Kim KH, Shin TM, Choi IG, Han SW, Hwang J, Koh I, Shin HD, Woo SI (2011) Association of RANBP1 haplotype with smooth pursuit eye movement abnormality. Am J Med Genet B Neuropsychiatr Genet 156B(1):67–71. doi:10.​1002/​ajmg.​b.​31139 PubMedCrossRef
38.
Zurück zum Zitat Shin HD, Park BL, Bae JS, Park TJ, Chun JY, Park CS, Sohn JW, Kim BJ, Kang YH, Kim JW, Kim KH, Shin TM, Woo SI (2010) Association of ZDHHC8 polymorphisms with smooth pursuit eye movement abnormality. Am J Med Genet B Neuropsychiatr Genet 153B(6):1167–1172. doi:10.1002/ajmg.b.31083 PubMed Shin HD, Park BL, Bae JS, Park TJ, Chun JY, Park CS, Sohn JW, Kim BJ, Kang YH, Kim JW, Kim KH, Shin TM, Woo SI (2010) Association of ZDHHC8 polymorphisms with smooth pursuit eye movement abnormality. Am J Med Genet B Neuropsychiatr Genet 153B(6):1167–1172. doi:10.​1002/​ajmg.​b.​31083 PubMed
39.
Zurück zum Zitat Arolt V, Lencer R, Purmann S, Schurmann M, Muller-Myhsok B, Krecker K, Schwinger E (1999) Testing for linkage of eye tracking dysfunction and schizophrenia to markers on chromosomes 6, 8, 9, 20, and 22 in families multiply affected with schizophrenia. Am J Med Genet 88(6):603–606PubMedCrossRef Arolt V, Lencer R, Purmann S, Schurmann M, Muller-Myhsok B, Krecker K, Schwinger E (1999) Testing for linkage of eye tracking dysfunction and schizophrenia to markers on chromosomes 6, 8, 9, 20, and 22 in families multiply affected with schizophrenia. Am J Med Genet 88(6):603–606PubMedCrossRef
40.
Zurück zum Zitat Pasaje CF, Bae JS, Park BL, Park CS, Kim BJ, Lee CS, Kim JW, Choi WH, Shin TM, Koh IS, Choi IG, Woo SL, Shin HD (2011) Lack of association of the RTN4R genetic variations with risk of schizophrenia and SPEM abnormality in a Korean population. Psychiatry Res 189(2):312–314. doi:10.1016/j.psychres.2011.02.006 PubMedCrossRef Pasaje CF, Bae JS, Park BL, Park CS, Kim BJ, Lee CS, Kim JW, Choi WH, Shin TM, Koh IS, Choi IG, Woo SL, Shin HD (2011) Lack of association of the RTN4R genetic variations with risk of schizophrenia and SPEM abnormality in a Korean population. Psychiatry Res 189(2):312–314. doi:10.​1016/​j.​psychres.​2011.​02.​006 PubMedCrossRef
41.
Zurück zum Zitat Wonodi I, Stine OC, Sathyasaikumar KV, Roberts RC, Mitchell BD, Hong LE, Kajii Y, Thaker GK, Schwarcz R (2011) Downregulated kynurenine 3-monooxygenase gene expression and enzyme activity in schizophrenia and genetic association with schizophrenia endophenotypes. Arch Gen Psychiatry 68(7):665–674. doi:10.1001/archgenpsychiatry.2011.71 PubMedCrossRef Wonodi I, Stine OC, Sathyasaikumar KV, Roberts RC, Mitchell BD, Hong LE, Kajii Y, Thaker GK, Schwarcz R (2011) Downregulated kynurenine 3-monooxygenase gene expression and enzyme activity in schizophrenia and genetic association with schizophrenia endophenotypes. Arch Gen Psychiatry 68(7):665–674. doi:10.​1001/​archgenpsychiatr​y.​2011.​71 PubMedCrossRef
42.
Zurück zum Zitat Jonsson EG, Nothen MM, Neidt H, Forslund K, Rylander G, Mattila-Evenden M, Asberg M, Propping P, Sedvall GC (1999) Association between a promoter polymorphism in the dopamine D2 receptor gene and schizophrenia. Schizophr Res 40(1):31–36PubMedCrossRef Jonsson EG, Nothen MM, Neidt H, Forslund K, Rylander G, Mattila-Evenden M, Asberg M, Propping P, Sedvall GC (1999) Association between a promoter polymorphism in the dopamine D2 receptor gene and schizophrenia. Schizophr Res 40(1):31–36PubMedCrossRef
44.
Zurück zum Zitat Egan MF, Straub RE, Goldberg TE, Yakub I, Callicott JH, Hariri AR, Mattay VS, Bertolino A, Hyde TM, Shannon-Weickert C, Akil M, Crook J, Vakkalanka RK, Balkissoon R, Gibbs RA, Kleinman JE, Weinberger DR (2004) Variation in GRM3 affects cognition, prefrontal glutamate, and risk for schizophrenia. Proc Natl Acad Sci USA 101(34):12604–12609. doi:10.1073/pnas.0405077101 PubMedCentralPubMedCrossRef Egan MF, Straub RE, Goldberg TE, Yakub I, Callicott JH, Hariri AR, Mattay VS, Bertolino A, Hyde TM, Shannon-Weickert C, Akil M, Crook J, Vakkalanka RK, Balkissoon R, Gibbs RA, Kleinman JE, Weinberger DR (2004) Variation in GRM3 affects cognition, prefrontal glutamate, and risk for schizophrenia. Proc Natl Acad Sci USA 101(34):12604–12609. doi:10.​1073/​pnas.​0405077101 PubMedCentralPubMedCrossRef
47.
Zurück zum Zitat Baune BT, Suslow T, Beste C, Birosova E, Domschke K, Sehlmeyer C, Konrad C (2010) Association between genetic variants of the metabotropic glutamate receptor 3 (GRM3) and cognitive set shifting in healthy individuals. Genes, brain, behav 9(5):459–466. doi:10.1111/j.1601-183X.2010.00573.x Baune BT, Suslow T, Beste C, Birosova E, Domschke K, Sehlmeyer C, Konrad C (2010) Association between genetic variants of the metabotropic glutamate receptor 3 (GRM3) and cognitive set shifting in healthy individuals. Genes, brain, behav 9(5):459–466. doi:10.​1111/​j.​1601-183X.​2010.​00573.​x
48.
Zurück zum Zitat Sun W, McConnell E, Pare JF, Xu Q, Chen M, Peng W, Lovatt D, Han X, Smith Y, Nedergaard M (2013) Glutamate-dependent neuroglial calcium signaling differs between young and adult brain. Science (New York, NY) 339(6116):197–200. doi:10.1126/science.1226740 CrossRef Sun W, McConnell E, Pare JF, Xu Q, Chen M, Peng W, Lovatt D, Han X, Smith Y, Nedergaard M (2013) Glutamate-dependent neuroglial calcium signaling differs between young and adult brain. Science (New York, NY) 339(6116):197–200. doi:10.​1126/​science.​1226740 CrossRef
49.
Zurück zum Zitat Corripio I, Ferreira A, Portella MJ, Perez V, Escarti MJ, Del Valle Camacho M, Sauras RB, Alonso A, Grasa EM, Carrio I, Catafau AM, Alvarez E (2012) The role of striatal dopamine D2 receptors in the occurrence of extrapyramidal side effects: iodine-123-iodobenzamide single photon emission computed tomography study. Psychiatry Res 201(1):73–77. doi:10.1016/j.pscychresns.2011.02.004 PubMedCrossRef Corripio I, Ferreira A, Portella MJ, Perez V, Escarti MJ, Del Valle Camacho M, Sauras RB, Alonso A, Grasa EM, Carrio I, Catafau AM, Alvarez E (2012) The role of striatal dopamine D2 receptors in the occurrence of extrapyramidal side effects: iodine-123-iodobenzamide single photon emission computed tomography study. Psychiatry Res 201(1):73–77. doi:10.​1016/​j.​pscychresns.​2011.​02.​004 PubMedCrossRef
51.
Zurück zum Zitat Fijal BA, Kinon BJ, Kapur S, Stauffer VL, Conley RR, Jamal HH, Kane JM, Witte MM, Houston JP (2009) Candidate-gene association analysis of response to risperidone in African-American and white patients with schizophrenia. Pharmacogenomics J 9(5):311–318. doi:10.1038/tpj.2009.24 PubMedCrossRef Fijal BA, Kinon BJ, Kapur S, Stauffer VL, Conley RR, Jamal HH, Kane JM, Witte MM, Houston JP (2009) Candidate-gene association analysis of response to risperidone in African-American and white patients with schizophrenia. Pharmacogenomics J 9(5):311–318. doi:10.​1038/​tpj.​2009.​24 PubMedCrossRef
52.
Zurück zum Zitat First MB, Spitzer RL, Gibbon M, Williams JBW (1995) Structured clinical interview for DSM-IV axis I disorders, patient edition (SCID-P). New York State Psychiatric Institute, New York First MB, Spitzer RL, Gibbon M, Williams JBW (1995) Structured clinical interview for DSM-IV axis I disorders, patient edition (SCID-P). New York State Psychiatric Institute, New York
53.
Zurück zum Zitat Rhoades HM, Overall JE (1988) The semistructured BPRS interview and rating guide. Psychopharmacol Bull 24(1):101–104PubMed Rhoades HM, Overall JE (1988) The semistructured BPRS interview and rating guide. Psychopharmacol Bull 24(1):101–104PubMed
54.
Zurück zum Zitat The Psychological Corporation TP (1999) Wechsler abbreviated scale of intelligence (WASI) manual. The Psychological Corporation, San Antonio, TX The Psychological Corporation TP (1999) Wechsler abbreviated scale of intelligence (WASI) manual. The Psychological Corporation, San Antonio, TX
56.
Zurück zum Zitat Bishop JR, del Miller D, Ellingrod VL, Holman T (2011) Association between type-three metabotropic glutamate receptor gene (GRM3) variants and symptom presentation in treatment refractory schizophrenia. Hum Psychopharmacol 26(1):28–34. doi:10.1002/hup.1163 PubMedCentralPubMedCrossRef Bishop JR, del Miller D, Ellingrod VL, Holman T (2011) Association between type-three metabotropic glutamate receptor gene (GRM3) variants and symptom presentation in treatment refractory schizophrenia. Hum Psychopharmacol 26(1):28–34. doi:10.​1002/​hup.​1163 PubMedCentralPubMedCrossRef
59.
Zurück zum Zitat Tian C, Hinds DA, Shigeta R, Kittles R, Ballinger DG, Seldin MF (2006) A genomewide single-nucleotide-polymorphism panel with high ancestry information for African American admixture mapping. Am J Hum Genet 79(4):640–649PubMedCentralPubMedCrossRef Tian C, Hinds DA, Shigeta R, Kittles R, Ballinger DG, Seldin MF (2006) A genomewide single-nucleotide-polymorphism panel with high ancestry information for African American admixture mapping. Am J Hum Genet 79(4):640–649PubMedCentralPubMedCrossRef
60.
Zurück zum Zitat Giri VN, Egleston B, Ruth K, Uzzo RG, Chen DY, Buyyounouski M, Raysor S, Hooker S, Torres JB, Ramike T, Mastalski K, Kim TY, Kittles R (2009) Race, genetic West African ancestry, and prostate cancer prediction by prostate-specific antigen in prospectively screened high-risk men. Cancer Prev Res (Phila Pa) 2(3):244–250CrossRef Giri VN, Egleston B, Ruth K, Uzzo RG, Chen DY, Buyyounouski M, Raysor S, Hooker S, Torres JB, Ramike T, Mastalski K, Kim TY, Kittles R (2009) Race, genetic West African ancestry, and prostate cancer prediction by prostate-specific antigen in prospectively screened high-risk men. Cancer Prev Res (Phila Pa) 2(3):244–250CrossRef
61.
Zurück zum Zitat Hooker S, Hernandez W, Chen H, Robbins C, Torres JB, Ahaghotu C, Carpten J, Kittles RA (2010) Replication of prostate cancer risk loci on 8q24, 11q13, 17q12, 19q33, and Xp11 in African Americans. Prostate 70(3):270–275. doi:10.1002/pros.21061 PubMed Hooker S, Hernandez W, Chen H, Robbins C, Torres JB, Ahaghotu C, Carpten J, Kittles RA (2010) Replication of prostate cancer risk loci on 8q24, 11q13, 17q12, 19q33, and Xp11 in African Americans. Prostate 70(3):270–275. doi:10.​1002/​pros.​21061 PubMed
63.
Zurück zum Zitat Kupfer SS, Torres JB, Hooker S, Anderson JR, Skol AD, Ellis NA, Kittles RA (2009) Novel single nucleotide polymorphism associations with colorectal cancer on chromosome 8q24 in African and European Americans. Carcinogenesis 30(8):1353–1357. doi:10.1093/carcin/bgp123 PubMedCentralPubMedCrossRef Kupfer SS, Torres JB, Hooker S, Anderson JR, Skol AD, Ellis NA, Kittles RA (2009) Novel single nucleotide polymorphism associations with colorectal cancer on chromosome 8q24 in African and European Americans. Carcinogenesis 30(8):1353–1357. doi:10.​1093/​carcin/​bgp123 PubMedCentralPubMedCrossRef
64.
Zurück zum Zitat Falush D, Stephens M, Pritchard JK (2003) Inference of population structure using multilocus genotype data: linked loci and correlated allele frequencies. Genetics 164(4):1567–1587PubMedCentralPubMed Falush D, Stephens M, Pritchard JK (2003) Inference of population structure using multilocus genotype data: linked loci and correlated allele frequencies. Genetics 164(4):1567–1587PubMedCentralPubMed
65.
Zurück zum Zitat Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81(3):559–575. doi:10.1086/519795 PubMedCentralPubMedCrossRef Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81(3):559–575. doi:10.​1086/​519795 PubMedCentralPubMedCrossRef
67.
Zurück zum Zitat Arinami T, Gao M, Hamaguchi H, Toru M (1997) A functional polymorphism in the promoter region of the dopamine D2 receptor gene is associated with schizophrenia. Hum Mol Genet 6(4):577–582PubMedCrossRef Arinami T, Gao M, Hamaguchi H, Toru M (1997) A functional polymorphism in the promoter region of the dopamine D2 receptor gene is associated with schizophrenia. Hum Mol Genet 6(4):577–582PubMedCrossRef
68.
Zurück zum Zitat Jonsson EG, Nothen MM, Grunhage F, Farde L, Nakashima Y, Propping P, Sedvall GC (1999) Polymorphisms in the dopamine D2 receptor gene and their relationships to striatal dopamine receptor density of healthy volunteers. Mol Psychiatry 4(3):290–296PubMedCrossRef Jonsson EG, Nothen MM, Grunhage F, Farde L, Nakashima Y, Propping P, Sedvall GC (1999) Polymorphisms in the dopamine D2 receptor gene and their relationships to striatal dopamine receptor density of healthy volunteers. Mol Psychiatry 4(3):290–296PubMedCrossRef
69.
Zurück zum Zitat Cordeiro Q, Siqueira-Roberto J, Zung S, Vallada H (2009) Association between the DRD2−141C insertion/deletion polymorphism and schizophrenia. Arq Neuropsiquiatr 67(2A):191–194PubMedCrossRef Cordeiro Q, Siqueira-Roberto J, Zung S, Vallada H (2009) Association between the DRD2−141C insertion/deletion polymorphism and schizophrenia. Arq Neuropsiquiatr 67(2A):191–194PubMedCrossRef
70.
Zurück zum Zitat Li T, Arranz M, Aitchison KJ, Bryant C, Liu X, Kerwin RW, Murray R, Sham P, Collier DA (1998) Case-control, haplotype relative risk and transmission disequilibrium analysis of a dopamine D2 receptor functional promoter polymorphism in schizophrenia. Schizophr Res 32(2):87–92PubMedCrossRef Li T, Arranz M, Aitchison KJ, Bryant C, Liu X, Kerwin RW, Murray R, Sham P, Collier DA (1998) Case-control, haplotype relative risk and transmission disequilibrium analysis of a dopamine D2 receptor functional promoter polymorphism in schizophrenia. Schizophr Res 32(2):87–92PubMedCrossRef
71.
Zurück zum Zitat Stober G, Jatzke S, Heils A, Jungkunz G, Knapp M, Mossner R, Riederer P, Lesch KP (1998) Insertion/deletion variant (−141C Ins/Del) in the 5′ regulatory region of the dopamine D2 receptor gene: lack of association with schizophrenia and bipolar affective disorder. Short communication. J neural transm 105(1):101–109PubMedCrossRef Stober G, Jatzke S, Heils A, Jungkunz G, Knapp M, Mossner R, Riederer P, Lesch KP (1998) Insertion/deletion variant (−141C Ins/Del) in the 5′ regulatory region of the dopamine D2 receptor gene: lack of association with schizophrenia and bipolar affective disorder. Short communication. J neural transm 105(1):101–109PubMedCrossRef
72.
Zurück zum Zitat Lencer R, Keedy SK, Reilly JL, McDonough BE, Harris MS, Sprenger A, Sweeney JA (2011) Altered transfer of visual motion information to parietal association cortex in untreated first-episode psychosis: implications for pursuit eye tracking. Psychiatry Res 194(1):30–38PubMedCentralPubMedCrossRef Lencer R, Keedy SK, Reilly JL, McDonough BE, Harris MS, Sprenger A, Sweeney JA (2011) Altered transfer of visual motion information to parietal association cortex in untreated first-episode psychosis: implications for pursuit eye tracking. Psychiatry Res 194(1):30–38PubMedCentralPubMedCrossRef
75.
Zurück zum Zitat Dalvie S, Horn N, Nossek C, van der Merwe L, Stein DJ, Ramesar R (2010) Psychosis and relapse in bipolar disorder are related to GRM3, DAOA, and GRIN2B genotype. Afr J Psychiatry 13(4):297–301 Dalvie S, Horn N, Nossek C, van der Merwe L, Stein DJ, Ramesar R (2010) Psychosis and relapse in bipolar disorder are related to GRM3, DAOA, and GRIN2B genotype. Afr J Psychiatry 13(4):297–301
77.
Zurück zum Zitat Corti C, Xuereb JH, Corsi M, Ferraguti F (2001) Identification and characterization of the promoter region of the GRM3 gene. Biochem Biophys Res Commun 286(2):381–387. doi:10.1006/bbrc 2001.5391PubMedCrossRef Corti C, Xuereb JH, Corsi M, Ferraguti F (2001) Identification and characterization of the promoter region of the GRM3 gene. Biochem Biophys Res Commun 286(2):381–387. doi:10.​1006/​bbrc 2001.5391PubMedCrossRef
78.
Zurück zum Zitat Fujii Y, Shibata H, Kikuta R, Makino C, Tani A, Hirata N, Shibata A, Ninomiya H, Tashiro N, Fukumaki Y (2003) Positive associations of polymorphisms in the metabotropic glutamate receptor type 3 gene (GRM3) with schizophrenia. Psychiatr Genet 13(2):71–76. doi:10.1097/01.ypg.0000056682.82896.b0 PubMed Fujii Y, Shibata H, Kikuta R, Makino C, Tani A, Hirata N, Shibata A, Ninomiya H, Tashiro N, Fukumaki Y (2003) Positive associations of polymorphisms in the metabotropic glutamate receptor type 3 gene (GRM3) with schizophrenia. Psychiatr Genet 13(2):71–76. doi:10.​1097/​01.​ypg.​0000056682.​82896.​b0 PubMed
79.
Zurück zum Zitat Mossner R, Schuhmacher A, Schulze-Rauschenbach S, Kuhn KU, Rujescu D, Rietschel M, Zobel A, Franke P, Wolwer W, Gaebel W, Hafner H, Wagner M, Maier W (2008) Further evidence for a functional role of the glutamate receptor gene GRM3 in schizophrenia. Eur Neuropsychopharmacol 18(10):768–772. doi:10.1016/j.euroneuro.2008.05.007 PubMedCrossRef Mossner R, Schuhmacher A, Schulze-Rauschenbach S, Kuhn KU, Rujescu D, Rietschel M, Zobel A, Franke P, Wolwer W, Gaebel W, Hafner H, Wagner M, Maier W (2008) Further evidence for a functional role of the glutamate receptor gene GRM3 in schizophrenia. Eur Neuropsychopharmacol 18(10):768–772. doi:10.​1016/​j.​euroneuro.​2008.​05.​007 PubMedCrossRef
80.
Zurück zum Zitat Schwab SG, Plummer C, Albus M, Borrmann-Hassenbach M, Lerer B, Trixler M, Maier W, Wildenauer DB (2008) DNA sequence variants in the metabotropic glutamate receptor 3 and risk to schizophrenia: an association study. Psychiatr Genet 18(1):25–30. doi:10.1097/YPG.0b013e3282ef48d9 PubMedCrossRef Schwab SG, Plummer C, Albus M, Borrmann-Hassenbach M, Lerer B, Trixler M, Maier W, Wildenauer DB (2008) DNA sequence variants in the metabotropic glutamate receptor 3 and risk to schizophrenia: an association study. Psychiatr Genet 18(1):25–30. doi:10.​1097/​YPG.​0b013e3282ef48d9​ PubMedCrossRef
81.
Zurück zum Zitat Callicott JH, Egan MF, Mattay VS, Bertolino A, Bone AD, Verchinksi B, Weinberger DR (2003) Abnormal fMRI response of the dorsolateral prefrontal cortex in cognitively intact siblings of patients with schizophrenia. Am J Psychiatry 160(4):709–719PubMedCrossRef Callicott JH, Egan MF, Mattay VS, Bertolino A, Bone AD, Verchinksi B, Weinberger DR (2003) Abnormal fMRI response of the dorsolateral prefrontal cortex in cognitively intact siblings of patients with schizophrenia. Am J Psychiatry 160(4):709–719PubMedCrossRef
82.
Zurück zum Zitat Nagel M, Sprenger A, Nitschke M, Zapf S, Heide W, Binkofski F, Lencer R (2007) Different extraretinal neuronal mechanisms of smooth pursuit eye movements in schizophrenia: an fMRI study. Neuroimage 34(1):300–309PubMedCrossRef Nagel M, Sprenger A, Nitschke M, Zapf S, Heide W, Binkofski F, Lencer R (2007) Different extraretinal neuronal mechanisms of smooth pursuit eye movements in schizophrenia: an fMRI study. Neuroimage 34(1):300–309PubMedCrossRef
Metadaten
Titel
Association of variants in DRD2 and GRM3 with motor and cognitive function in first-episode psychosis
verfasst von
Rebekka Lencer
Jeffrey R. Bishop
Margret S. H. Harris
James L. Reilly
Shitalben Patel
Rick Kittles
Konasale M. Prasad
Vishwajit L. Nimgaonkar
Matcheri S. Keshavan
John A. Sweeney
Publikationsdatum
01.06.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
European Archives of Psychiatry and Clinical Neuroscience / Ausgabe 4/2014
Print ISSN: 0940-1334
Elektronische ISSN: 1433-8491
DOI
https://doi.org/10.1007/s00406-013-0464-6

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