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Psychological Medicine Psychological Medicine

Article contents

Combined effect of genetic variants in the GluN2B coding gene (GRIN2B) on prefrontal function during working memory performance

Published online by Cambridge University Press:  22 December 2015

G. Pergola ,
P. Di Carlo ,
I. Andriola ,
B. Gelao ,
S. Torretta ,
M. T. Attrotto ,
L. Fazio ,
A. Raio ,
D. Albergo ,
R. Masellis ,
A. Rampino ,
G. Blasi  and
A. Bertolino
G. Pergola
Affiliation:
Department of Basic Medical Sciences, Neuroscience and Sensory Organs, University of Bari ‘Aldo Moro’, Piazza Giulio Cesare 11, 70124 Bari, Italy
P. Di Carlo
Affiliation:
Department of Basic Medical Sciences, Neuroscience and Sensory Organs, University of Bari ‘Aldo Moro’, Piazza Giulio Cesare 11, 70124 Bari, Italy
I. Andriola
Affiliation:
Department of Basic Medical Sciences, Neuroscience and Sensory Organs, University of Bari ‘Aldo Moro’, Piazza Giulio Cesare 11, 70124 Bari, Italy
B. Gelao
Affiliation:
Department of Basic Medical Sciences, Neuroscience and Sensory Organs, University of Bari ‘Aldo Moro’, Piazza Giulio Cesare 11, 70124 Bari, Italy
S. Torretta
Affiliation:
Department of Basic Medical Sciences, Neuroscience and Sensory Organs, University of Bari ‘Aldo Moro’, Piazza Giulio Cesare 11, 70124 Bari, Italy
M. T. Attrotto
Affiliation:
Department of Basic Medical Sciences, Neuroscience and Sensory Organs, University of Bari ‘Aldo Moro’, Piazza Giulio Cesare 11, 70124 Bari, Italy
L. Fazio
Affiliation:
Department of Basic Medical Sciences, Neuroscience and Sensory Organs, University of Bari ‘Aldo Moro’, Piazza Giulio Cesare 11, 70124 Bari, Italy
A. Raio
Affiliation:
Department of Basic Medical Sciences, Neuroscience and Sensory Organs, University of Bari ‘Aldo Moro’, Piazza Giulio Cesare 11, 70124 Bari, Italy
D. Albergo
Affiliation:
Department of Basic Medical Sciences, Neuroscience and Sensory Organs, University of Bari ‘Aldo Moro’, Piazza Giulio Cesare 11, 70124 Bari, Italy
R. Masellis
Affiliation:
Department of Basic Medical Sciences, Neuroscience and Sensory Organs, University of Bari ‘Aldo Moro’, Piazza Giulio Cesare 11, 70124 Bari, Italy Psychiatry Unit, Bari University Hospital, Piazza Giulio Cesare 11, 70124 Bari, Italy
A. Rampino
Affiliation:
Department of Basic Medical Sciences, Neuroscience and Sensory Organs, University of Bari ‘Aldo Moro’, Piazza Giulio Cesare 11, 70124 Bari, Italy Psychiatry Unit, Bari University Hospital, Piazza Giulio Cesare 11, 70124 Bari, Italy
G. Blasi
Affiliation:
Department of Basic Medical Sciences, Neuroscience and Sensory Organs, University of Bari ‘Aldo Moro’, Piazza Giulio Cesare 11, 70124 Bari, Italy Psychiatry Unit, Bari University Hospital, Piazza Giulio Cesare 11, 70124 Bari, Italy
A. Bertolino
Affiliation:
Department of Basic Medical Sciences, Neuroscience and Sensory Organs, University of Bari ‘Aldo Moro’, Piazza Giulio Cesare 11, 70124 Bari, Italy Psychiatry Unit, Bari University Hospital, Piazza Giulio Cesare 11, 70124 Bari, Italy NORD DTA, pRED, Hoffman – La Roche Ltd, Grenzacherstrasse 183, Basel, Switzerland
Corresponding
E-mail address:
alessandro.bertolino@uniba.it
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Abstract

Background

The GluN2B subunit of N-methyl-d-aspartate receptors is crucially involved in the physiology of the prefrontal cortex during working memory (WM). Consistently, genetic variants in the GluN2B coding gene (GRIN2B) have been associated with cognitive phenotypes. However, it is unclear how GRIN2B genetic variation affects gene expression and prefrontal cognitive processing. Using a composite score, we tested the combined effect of GRIN2B variants on prefrontal activity during WM performance in healthy subjects.

Method

We computed a composite score to combine the effects of single nucleotide polymorphisms on post-mortem prefrontal GRIN2B mRNA expression. We then computed the composite score in independent samples of healthy participants in a peripheral blood expression study (n = 46), in a WM behavioural study (n = 116) and in a WM functional magnetic resonance imaging study (n = 122).

Results

Five polymorphisms were associated with GRIN2B expression: rs2160517, rs219931, rs11055792, rs17833967 and rs12814951 (all corrected p < 0.05). The score computed to account for their combined effect reliably indexed gene expression. GRIN2B composite score correlated negatively with intelligence quotient, WM behavioural efficiency and dorsolateral prefrontal cortex activity. Moreover, there was a non-linear association between GRIN2B genetic score and prefrontal activity, i.e. both high and low putative genetic score levels were associated with high blood oxygen level-dependent signals in the prefrontal cortex.

Conclusions

Multiple genetic variants in GRIN2B are jointly associated with gene expression, prefrontal function and behaviour during WM. These results support the role of GRIN2B genetic variants in WM prefrontal activity in human adults.

Keywords

Expression quantitative trait loci GRIN2B N-methyl-d-aspartate prefrontal cortex working memory
Type
Original Articles
Information
Psychological Medicine , Volume 46 , Issue 6 , April 2016 , pp. 1135 - 1150
Copyright
Copyright © Cambridge University Press 2015 

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References

Alonso, P, Gratacos, M, Segalas, C, Escaramis, G, Real, E, Bayes, M, Labad, J, Lopez-Sola, C, Estivill, X, Menchon, JM (2012). Association between the NMDA glutamate receptor GRIN2B gene and obsessive–compulsive disorder. Journal of Psychiatry and Neuroscience 37, 273–281.CrossRefGoogle ScholarPubMed
Andreoli, V, De Marco, EV, Trecroci, F, Cittadella, R, Di Palma, G, Gambardella, A (2014). Potential involvement of GRIN2B encoding the NMDA receptor subunit NR2B in the spectrum of Alzheimer's disease. Journal of Neural Transmission 121, 533–542.Google ScholarPubMed
Arnold, PD, Rosenberg, DR, Mundo, E, Tharmalingam, S, Kennedy, JL, Richter, MA (2004). Association of a glutamate (NMDA) subunit receptor gene (GRIN2B) with obsessive–compulsive disorder: a preliminary study. Psychopharmacology (Berlin) 174, 530–538.CrossRefGoogle ScholarPubMed
Avramopoulos, D, Lasseter, VK, Fallin, MD, Wolyniec, PS, McGrath, JA, Nestadt, G, Valle, D, Pulver, AE (2007). Stage II follow-up on a linkage scan for bipolar disorder in the Ashkenazim provides suggestive evidence for chromosome 12p and the GRIN2B gene. Genetics in Medicine 9, 745–751.CrossRefGoogle ScholarPubMed
Benjamini, Y, Hochberg, Y (2000). On the adaptive control of the false discovery rate in multiple testing with independent statistics. Journal of Educational and Behavioral Statistics 25, 60–83.CrossRefGoogle Scholar
Bertolino, A, Caforio, G, Blasi, G, De Candia, M, Latorre, V, Petruzzella, V, Altamura, M, Nappi, G, Papa, S, Callicott, JH, Mattay, VS, Bellomo, A, Scarabino, T, Weinberger, DR, Nardini, M (2004). Interaction of COMT (Val(108/158)Met) genotype and olanzapine treatment on prefrontal cortical function in patients with schizophrenia. American Journal of Psychiatry 161, 1798–1805.CrossRefGoogle Scholar
Birnbaum, R, Weinberger, DR (2013). Functional neuroimaging and schizophrenia: a view towards effective connectivity modeling and polygenic risk. Dialogues in Clinical Neuroscience 15, 279–289.Google ScholarPubMed
Blasi, G, Napolitano, F, Ursini, G, Di Giorgio, A, Caforio, G, Taurisano, P, Fazio, L, Gelao, B, Attrotto, MT, Colagiorgio, L, Todarello, G, Piva, F, Papazacharias, A, Masellis, R, Mancini, M, Porcelli, A, Romano, R, Rampino, A, Quarto, T, Giulietti, M, Lipska, BK, Kleinman, JE, Popolizio, T, Weinberger, DR, Usiello, A, Bertolino, A (2013). Association of GSK-3β genetic variation with GSK-3β expression, prefrontal cortical thickness, prefrontal physiology, and schizophrenia. American Journal of Psychiatry 170, 868–876.CrossRefGoogle Scholar
Burns, M, Valdivia, H (2008). A simulation approach to assess the minimal number of real-time PCR replicates for GM quantification. European Food Research and Technology 227, 1721–1727.CrossRefGoogle Scholar
Cai, J, Zhang, W, Yi, Z, Lu, W, Wu, Z, Chen, J, Yu, S, Fang, Y, Zhang, C (2013). Influence of polymorphisms in genes SLC1A1, GRIN2B, and GRIK2 on clozapine-induced obsessive–compulsive symptoms. Psychopharmacology (Berlin) 230, 49–55.CrossRefGoogle ScholarPubMed
Callicott, JH, Bertolino, A, Mattay, VS, Langheim, FJ, Duyn, J, Coppola, R, Goldberg, TE, Weinberger, DR (2000). Physiological dysfunction of the dorsolateral prefrontal cortex in schizophrenia revisited. Cerebral Cortex 10, 1078–1092.CrossRefGoogle ScholarPubMed
Callicott, JH, Mattay, VS, Bertolino, A, Finn, K, Coppola, R, Frank, JA, Goldberg, TE, Weinberger, DR (1999). Physiological characteristics of capacity constraints in working memory as revealed by functional MRI. Cerebral Cortex 9, 20–26.CrossRefGoogle ScholarPubMed
Callicott, JH, Mattay, VS, Verchinski, BA, Marenco, S, Egan, MF, Weinberger, DR (2003). Complexity of prefrontal cortical dysfunction in schizophrenia: more than up or down. American Journal of Psychiatry 160, 2209–2215.CrossRefGoogle ScholarPubMed
Callicott, JH, Weinberger, DR (1999). Neuropsychiatric dynamics: the study of mental illness using functional magnetic resonance imaging. European Journal of Radiology 30, 95–104.CrossRefGoogle ScholarPubMed
Cao, X, Cui, Z, Feng, R, Tang, YP, Qin, Z, Mei, B, Tsien, JZ (2007). Maintenance of superior learning and memory function in NR2B transgenic mice during ageing. European Journal of Neuroscience 25, 1815–1822.CrossRefGoogle ScholarPubMed
Chen, C, Li, X, Wang, T, Wang, HH, Fu, Y, Zhang, L, Xiao, SF (2010). Association between NMDA receptor subunit 2b gene polymorphism and Alzheimer's disease in Chinese Han population in Shanghai. Neuroscience Bulletin 26, 395–400.CrossRefGoogle ScholarPubMed
Clinton, SM, Haroutunian, V, Meador-Woodruff, JH (2006). Up-regulation of NMDA receptor subunit and post-synaptic density protein expression in the thalamus of elderly patients with schizophrenia. Journal of Neurochemistry 98, 1114–1125.CrossRefGoogle ScholarPubMed
Colantuoni, C, Lipska, BK, Ye, T, Hyde, TM, Tao, R, Leek, JT, Colantuoni, EA, Elkahloun, AG, Herman, MM, Weinberger, DR, Kleinman, JE (2011). Temporal dynamics and genetic control of transcription in the human prefrontal cortex. Nature 478, 519–523.CrossRefGoogle ScholarPubMed
Constantine-Paton, M, Cline, HT (1998). LTP and activity-dependent synaptogenesis: the more alike they are, the more different they become. Current Opinion in Neurobiology 8, 139–148.CrossRefGoogle ScholarPubMed
Cools, R, D'Esposito, M (2011). Inverted U-shaped dopamine actions on human working memory and cognitive control. Biological Psychiatry 69, e113–e125.CrossRefGoogle ScholarPubMed
Cull-Candy, S, Brickley, S, Farrant, M (2001). NMDA receptor subunits: diversity, development and disease. Current Opinion in Neurobiology 11, 327–335.CrossRefGoogle ScholarPubMed
Cull-Candy, SG, Leszkiewicz, DN (2004). Role of distinct NMDA receptor subtypes at central synapses. Science's STKE 2004, re16.Google ScholarPubMed
De Jager, PL, Chibnik, LB, Cui, J, Reischl, J, Lehr, S, Simon, KC, Aubin, C, Bauer, D, Heubach, JF, Sandbrink, R, Tyblova, M, Lelkova, P, Havrdova, E, Pohl, C, Horakova, D, Ascherio, A, Hafler, DA, Karlson, EW (2009). Integration of genetic risk factors into a clinical algorithm for multiple sclerosis susceptibility: a weighted genetic risk score. Lancet Neurology 8, 1111–1119.CrossRefGoogle ScholarPubMed
Demontis, D, Nyegaard, M, Buttenschon, HN, Hedemand, A, Pedersen, CB, Grove, J, Flint, TJ, Nordentoft, M, Werge, T, Hougaard, DM, Sorensen, KM, Yolken, RH, Mors, O, Borglum, AD, Mortensen, PB (2011). Association of GRIN1 and GRIN2A-D with schizophrenia and genetic interaction with maternal herpes simplex virus-2 infection affecting disease risk. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 156B, 913–922.CrossRefGoogle ScholarPubMed
Di Maria, E, Gulli, R, Begni, S, De Luca, A, Bignotti, S, Pasini, A, Bellone, E, Pizzuti, A, Dallapiccola, B, Novelli, G, Ajmar, F, Gennarelli, M, Mandich, P (2004). Variations in the NMDA receptor subunit 2B gene (GRIN2B) and schizophrenia: a case–control study. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 128B, 27–29.CrossRefGoogle ScholarPubMed
Dumas, TC (2005). Developmental regulation of cognitive abilities: modified composition of a molecular switch turns on associative learning. Progress in Neurobiology 76, 189–211.CrossRefGoogle ScholarPubMed
Dumitriu, D, Hao, J, Hara, Y, Kaufmann, J, Janssen, WG, Lou, W, Rapp, PR, Morrison, JH (2010). Selective changes in thin spine density and morphology in monkey prefrontal cortex correlate with aging-related cognitive impairment. Journal of Neuroscience 30, 7507–7515.CrossRefGoogle ScholarPubMed
Egan, MF, Goldberg, TE, Gscheidle, T, Weirich, M, Rawlings, R, Hyde, TM, Bigelow, L, Weinberger, DR (2001). Relative risk for cognitive impairments in siblings of patients with schizophrenia. Biological Psychiatry 50, 98–107.CrossRefGoogle ScholarPubMed
Endele, S, Rosenberger, G, Geider, K, Popp, B, Tamer, C, Stefanova, I, Milh, M, Kortum, F, Fritsch, A, Pientka, FK, Hellenbroich, Y, Kalscheuer, VM, Kohlhase, J, Moog, U, Rappold, G, Rauch, A, Ropers, HH, von Spiczak, S, Tonnies, H, Villeneuve, N, Villard, L, Zabel, B, Zenker, M, Laube, B, Reis, A, Wieczorek, D, Van Maldergem, L, Kutsche, K (2010). Mutations in GRIN2A and GRIN2B encoding regulatory subunits of NMDA receptors cause variable neurodevelopmental phenotypes. Nature Genetics 42, 1021–1026.CrossRefGoogle ScholarPubMed
Engstrom, K, Vahter, M, Mlakar, SJ, Concha, G, Nermell, B, Raqib, R, Cardozo, A, Broberg, K (2011). Polymorphisms in arsenic(+III oxidation state) methyltransferase (AS3MT) predict gene expression of AS3MT as well as arsenic metabolism. Environmental Health Perspectives 119, 182–188.CrossRefGoogle ScholarPubMed
Fallin, MD, Lasseter, VK, Avramopoulos, D, Nicodemus, KK, Wolyniec, PS, McGrath, JA, Steel, G, Nestadt, G, Liang, KY, Huganir, RL, Valle, D, Pulver, AE (2005). Bipolar I disorder and schizophrenia: a 440-single-nucleotide polymorphism screen of 64 candidate genes among Ashkenazi Jewish case–parent trios. American Journal of Human Genetics 77, 918–936.CrossRefGoogle ScholarPubMed
Flores-Barrera, E, Thomases, DR, Heng, LJ, Cass, DK, Caballero, A, Tseng, KY (2014). Late adolescent expression of GluN2B transmission in the prefrontal cortex is input-specific and requires postsynaptic protein kinase A and D1 dopamine receptor signaling. Biological Psychiatry 75, 508–516.CrossRefGoogle ScholarPubMed
Gilmartin, MR, Miyawaki, H, Helmstetter, FJ, Diba, K (2013). Prefrontal activity links nonoverlapping events in memory. Journal of Neuroscience 33, 10910–10914.CrossRefGoogle ScholarPubMed
Goldman-Rakic, PS (1995). Architecture of the prefrontal cortex and the central executive. Annals of the New York Academy of Sciences 769, 71–83.CrossRefGoogle ScholarPubMed
Goldman-Rakic, PS, Muly, EC 3rd, Williams, GV (2000). D1 receptors in prefrontal cells and circuits. Brain Research Reviews 31, 295–301.CrossRefGoogle ScholarPubMed
Green, DM, Swets, JA (1966). Signal Detection Theory and Psychophysics. Wiley & Sons, Inc.: New York.Google Scholar
Hardingham, GE, Bading, H (2003). The Yin and Yang of NMDA receptor signalling. Trends in Neurosciences 26, 81–89.CrossRefGoogle ScholarPubMed
Jiang, H, Jia, J (2009). Association between NR2B subunit gene (GRIN2B) promoter polymorphisms and sporadic Alzheimer's disease in the North Chinese population. Neuroscience Letters 450, 356–360.CrossRefGoogle ScholarPubMed
Kayadjanian, N, Heavens, RP, Besson, MJ, Sirinathsinghji, DJ (1996). Striatal NMDAR2B mRNA expression after bilateral cortical and unilateral nigral deafferentation. Neuroreport 7, 713–716.CrossRefGoogle ScholarPubMed
Kenny, EM, Cormican, P, Furlong, S, Heron, E, Kenny, G, Fahey, C, Kelleher, E, Ennis, S, Tropea, D, Anney, R, Corvin, AP, Donohoe, G, Gallagher, L, Gill, M, Morris, DW (2014). Excess of rare novel loss-of-function variants in synaptic genes in schizophrenia and autism spectrum disorders. Molecular Psychiatry 19, 872–879.CrossRefGoogle ScholarPubMed
Koronyo-Hamaoui, M, Frisch, A, Stein, D, Denziger, Y, Leor, S, Michaelovsky, E, Laufer, N, Carel, C, Fennig, S, Mimouni, M, Ram, A, Zubery, E, Jeczmien, P, Apter, A, Weizman, A, Gak, E (2007). Dual contribution of NR2B subunit of NMDA receptor and SK3 Ca2+-activated K+ channel to genetic predisposition to anorexia nervosa. Journal of Psychiatric Research 41, 160–167.CrossRefGoogle Scholar
Kristiansen, LV, Patel, SA, Haroutunian, V, Meador-Woodruff, JH (2010). Expression of the NR2B-NMDA receptor subunit and its Tbr-1/CINAP regulatory proteins in postmortem brain suggest altered receptor processing in schizophrenia. Synapse 64, 495–502.CrossRefGoogle Scholar
Lacadie, CM, Fulbright, RK, Rajeevan, N, Constable, RT, Papademetris, X (2008). More accurate Talairach coordinates for neuroimaging using non-linear registration. NeuroImage 42, 717–725.CrossRefGoogle ScholarPubMed
Lancaster, JL, Woldorff, MG, Parsons, LM, Liotti, M, Freitas, ES, Rainey, L, Kochunov, PV, Nickerson, D, Mikiten, SA, Fox, PT (2000). Automated Talairach Atlas labels for functional brain mapping. Human Brain Mapping 10, 120–131.3.0.CO;2-8>CrossRefGoogle ScholarPubMed
Liu, Y, Wong, TP, Aarts, M, Rooyakkers, A, Liu, L, Lai, TW, Wu, DC, Lu, J, Tymianski, M, Craig, AM, Wang, YT (2007). NMDA receptor subunits have differential roles in mediating excitotoxic neuronal death both in vitro and in vivo . Journal of Neuroscience 27, 2846–2857.CrossRefGoogle ScholarPubMed
Liu, L, Wong, TP, Pozza, MF, Lingenhoehl, K, Wang, Y, Sheng, M, Auberson, YP, Wang, YT (2004). Role of NMDA receptor subtypes in governing the direction of hippocampal synaptic plasticity. Science 304, 1021–1024.CrossRefGoogle ScholarPubMed
Livak, KJ, Schmittgen, TD (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(–delta delta CT) method. Methods 25, 402–408.CrossRefGoogle Scholar
Lorenzi, C, Delmonte, D, Pirovano, A, Marino, E, Bongiorno, F, Catalano, M, Colombo, C, Bramanti, P, Smeraldi, E (2010). Searching susceptibility loci for bipolar disorder: a sib pair study on chromosome 12. Neuropsychobiology 61, 10–18.CrossRefGoogle ScholarPubMed
Ludwig, KU, Roeske, D, Herms, S, Schumacher, J, Warnke, A, Plume, E, Neuhoff, N, Bruder, J, Remschmidt, H, Schulte-Korne, G, Muller-Myhsok, B, Nothen, MM, Hoffmann, P (2010). Variation in GRIN2B contributes to weak performance in verbal short-term memory in children with dyslexia. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 153B, 503–511.CrossRefGoogle ScholarPubMed
Martucci, L, Wong, AH, De Luca, V, Likhodi, O, Wong, GW, King, N, Kennedy, JL (2006). N-methyl-d-aspartate receptor NR2B subunit gene GRIN2B in schizophrenia and bipolar disorder: polymorphisms and mRNA levels. Schizophrenia Research 84, 214–221.CrossRefGoogle ScholarPubMed
Meyer-Lindenberg, A, Weinberger, DR (2006). Intermediate phenotypes and genetic mechanisms of psychiatric disorders. Nature Reviews Neuroscience 7, 818–827.CrossRefGoogle ScholarPubMed
Miyatake, R, Furukawa, A, Suwaki, H (2002). Identification of a novel variant of the human NR2B gene promoter region and its possible association with schizophrenia. Molecular Psychiatry 7, 1101–1106.CrossRefGoogle ScholarPubMed
Myers, RA, Casals, F, Gauthier, J, Hamdan, FF, Keebler, J, Boyko, AR, Bustamante, CD, Piton, AM, Spiegelman, D, Henrion, E, Zilversmit, M, Hussin, J, Quinlan, J, Yang, Y, Lafreniere, RG, Griffing, AR, Stone, EA, Rouleau, GA, Awadalla, P (2011). A population genetic approach to mapping neurological disorder genes using deep resequencing. PLoS Genetics 7, e1001318.CrossRefGoogle ScholarPubMed
Ness, V, Arning, L, Niesert, HE, Stuttgen, MC, Epplen, JT, Beste, C (2011). Variations in the GRIN2B gene are associated with risky decision-making. Neuropharmacology 61, 950–956.CrossRefGoogle ScholarPubMed
Nicodemus, KK, Hargreaves, A, Morris, D, Anney, R, Gill, M, Corvin, A, Donohoe, G (2014). Variability in working memory performance explained by epistasis vs polygenic scores in the ZNF804A pathway. JAMA Psychiatry 71, 778–785.CrossRefGoogle ScholarPubMed
O'Roak, BJ, Deriziotis, P, Lee, C, Vives, L, Schwartz, JJ, Girirajan, S, Karakoc, E, Mackenzie, AP, Ng, SB, Baker, C, Rieder, MJ, Nickerson, DA, Bernier, R, Fisher, SE, Shendure, J, Eichler, EE (2011). Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations. Nature Genetics 43, 585–589.CrossRefGoogle ScholarPubMed
Ohtsuki, T, Sakurai, K, Dou, H, Toru, M, Yamakawa-Kobayashi, K, Arinami, T (2001). Mutation analysis of the NMDAR2B (GRIN2B) gene in schizophrenia. Molecular Psychiatry 6, 211–216.CrossRefGoogle Scholar
Oldfield, RC (1971). The assessment and analysis of handedness: The Edinburgh Inventory. Neuropsychologia 9, 97–113.CrossRefGoogle ScholarPubMed
Paoletti, P, Neyton, J (2007). NMDA receptor subunits: function and pharmacology. Current Opinion in Pharmacology 7, 39–47.CrossRefGoogle ScholarPubMed
Purcell, SM, Wray, NR, Stone, JL, Visscher, PM, O'Donovan, MC, Sullivan, PF, Sklar, P (2009). Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 460, 748–752.Google ScholarPubMed
Qiang, M, Rani, CS, Ticku, MK (2005). Neuron-restrictive silencer factor regulates the N-methyl-d-aspartate receptor 2B subunit gene in basal and ethanol-induced gene expression in fetal cortical neurons. Molecular Pharmacology 67, 2115–2125.CrossRefGoogle ScholarPubMed
R Development Core T (2014). R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing: Vienna, Austria.Google Scholar
Rodenas-Ruano, A, Chavez, AE, Cossio, MJ, Castillo, PE, Zukin, RS (2012). REST-dependent epigenetic remodeling promotes the developmental switch in synaptic NMDA receptors. Nature Neuroscience 15, 1382–1390.CrossRefGoogle ScholarPubMed
Rottschy, C, Langner, R, Dogan, I, Reetz, K, Laird, AR, Schulz, JB, Fox, PT, Eickhoff, SB (2012). Modelling neural correlates of working memory: a coordinate-based meta-analysis. NeuroImage 60, 830–846.CrossRefGoogle ScholarPubMed
Sasner, M, Buonanno, A (1996). Distinct N-methyl-d-aspartate receptor 2B subunit gene sequences confer neural and developmental specific expression. Journal of Biological Chemistry 271, 21316–21322.CrossRefGoogle ScholarPubMed
Schito, AM, Pizzuti, A, Di Maria, E, Schenone, A, Ratti, A, Defferrari, R, Bellone, E, Mancardi, GL, Ajmar, F, Mandich, P (1997). mRNA distribution in adult human brain of GRIN2B, a N-methyl-d-aspartate (NMDA) receptor subunit. Neuroscience Letters 239, 49–53.CrossRefGoogle ScholarPubMed
Schoenherr, CJ, Anderson, DJ (1995). Silencing is golden: negative regulation in the control of neuronal gene transcription. Current Opinion in Neurobiology 5, 566–571.CrossRefGoogle Scholar
Sokolowski, M, Ben-Efraim, YJ, Wasserman, J, Wasserman, D (2013). Glutamatergic GRIN2B and polyaminergic ODC1 genes in suicide attempts: associations and gene–environment interactions with childhood/adolescent physical assault. Molecular Psychiatry 18, 985–992.CrossRefGoogle ScholarPubMed
Stein, JL, Hua, X, Morra, JH, Lee, S, Hibar, DP, Ho, AJ, Leow, AD, Toga, AW, Sul, JH, Kang, HM, Eskin, E, Saykin, AJ, Shen, L, Foroud, T, Pankratz, N, Huentelman, MJ, Craig, DW, Gerber, JD, Allen, AN, Corneveaux, JJ, Stephan, DA, Webster, J, DeChairo, BM, Potkin, SG, Jack, CR Jr., Weiner, MW, Thompson, PM (2010). Genome-wide analysis reveals novel genes influencing temporal lobe structure with relevance to neurodegeneration in Alzheimer's disease. NeuroImage 51, 542–554.CrossRefGoogle ScholarPubMed
Stocca, G, Vicini, S (1998). Increased contribution of NR2A subunit to synaptic NMDA receptors in developing rat cortical neurons. Journal of Physiology 507, 13–24.CrossRefGoogle ScholarPubMed
Stone, M (1974). Cross-validatory choice and assessment of statistical predictions. Journal of the Royal Statistical Society. Series B (Methodological) 36, 111–147.Google Scholar
Sugiura, N, Patel, RG, Corriveau, RA (2001). N-methyl-d-aspartate receptors regulate a group of transiently expressed genes in the developing brain. Journal of Biological Chemistry 276, 14257–14263.CrossRefGoogle ScholarPubMed
Tang, YP, Shimizu, E, Dube, GR, Rampon, C, Kerchner, GA, Zhuo, M, Liu, G, Tsien, JZ (1999). Genetic enhancement of learning and memory in mice. Nature 401, 63–69.CrossRefGoogle ScholarPubMed
Tang, YP, Wang, H, Feng, R, Kyin, M, Tsien, JZ (2001). Differential effects of enrichment on learning and memory function in NR2B transgenic mice. Neuropharmacology 41, 779–790.CrossRefGoogle ScholarPubMed
Tesli, M, Espeseth, T, Bettella, F, Mattingsdal, M, Aas, M, Melle, I, Djurovic, S, Andreassen, OA (2014). Polygenic risk score and the psychosis continuum model. Acta Psychiatrica Scandinavica 130, 311–317.CrossRefGoogle ScholarPubMed
Ting, JT, Feng, G (2008). Glutamatergic synaptic dysfunction and obsessive–compulsive disorder. Current Chemical Genomics 2, 62–75.CrossRefGoogle ScholarPubMed
Traynelis, SF, Wollmuth, LP, McBain, CJ, Menniti, FS, Vance, KM, Ogden, KK, Hansen, KB, Yuan, H, Myers, SJ, Dingledine, R (2010). Glutamate receptor ion channels: structure, regulation, and function. Pharmacological Reviews 62, 405–496.CrossRefGoogle ScholarPubMed
von Engelhardt, J, Doganci, B, Jensen, V, Hvalby, O, Gongrich, C, Taylor, A, Barkus, C, Sanderson, DJ, Rawlins, JN, Seeburg, PH, Bannerman, DM, Monyer, H (2008). Contribution of hippocampal and extra-hippocampal NR2B-containing NMDA receptors to performance on spatial learning tasks. Neuron 60, 846–860.CrossRefGoogle ScholarPubMed
Walton, E, Turner, J, Gollub, RL, Manoach, DS, Yendiki, A, Ho, BC, Sponheim, SR, Calhoun, VD, Ehrlich, S (2013). Cumulative genetic risk and prefrontal activity in patients with schizophrenia. Schizophrenia Bulletin 39, 703–711.CrossRefGoogle ScholarPubMed
Wang, H, Stradtman, GG 3rd, Wang, XJ, Gao, WJ (2008). A specialized NMDA receptor function in layer 5 recurrent microcircuitry of the adult rat prefrontal cortex. Proceedings of the National Academy of Sciences USA 105, 16791–16796.CrossRefGoogle ScholarPubMed
Wang, M, Yang, Y, Wang, CJ, Gamo, NJ, Jin, LE, Mazer, JA, Morrison, JH, Wang, XJ, Arnsten, AF (2013). NMDA receptors subserve persistent neuronal firing during working memory in dorsolateral prefrontal cortex. Neuron 77, 736–749.CrossRefGoogle ScholarPubMed
Wechsler, D (1981). WAIS-R: Manual: Wechsler Adult Intelligence Scale-Revised. The Psychological Corporation: San Antonio, TX.Google Scholar
Weickert, CS, Fung, SJ, Catts, VS, Schofield, PR, Allen, KM, Moore, LT, Newell, KA, Pellen, D, Huang, XF, Catts, SV, Weickert, TW (2013). Molecular evidence of N-methyl-d-aspartate receptor hypofunction in schizophrenia. Molecular Psychiatry 18, 1185–1192.CrossRefGoogle Scholar
Weinberger, DR, Mattay, V, Callicott, JH, Kotrla, K, Santha, A, van Gelderen, P, Duyn, J, Moonen, C, Frank, J (1996). fMRI applications in schizophrenia research. NeuroImage 4, S118–S126.CrossRefGoogle ScholarPubMed
Whelan, R, Garavan, H (2014). When optimism hurts: inflated predictions in psychiatric neuroimaging. Biological Psychiatry 75, 746–748.CrossRefGoogle ScholarPubMed
Yoo, HJ, Cho, IH, Park, M, Yang, SY, Kim, SA (2012). Family based association of GRIN2A and GRIN2B with Korean autism spectrum disorders. Neuroscience Letters 512, 89–93.CrossRefGoogle ScholarPubMed
Zhang, C, Li, Z, Wu, Z, Chen, J, Wang, Z, Peng, D, Hong, W, Yuan, C, Yu, S, Xu, Y, Xu, L, Xiao, Z, Fang, Y (2014). A study of N-methyl-d-aspartate receptor gene (GRIN2B) variants as predictors of treatment-resistant major depression. Psychopharmacology (Berlin) 231, 685–693.CrossRefGoogle ScholarPubMed
Zhao, Q, Che, R, Zhang, Z, Wang, P, Li, J, Li, Y, Huang, K, Tang, W, Feng, G, Lindpaintner, K, He, L, Shi, Y (2011). Positive association between GRIN2B gene and bipolar disorder in the Chinese Han Population. Psychiatry Research 185, 290–292.CrossRefGoogle ScholarPubMed
Zhou, M, Baudry, M (2006). Developmental changes in NMDA neurotoxicity reflect developmental changes in subunit composition of NMDA receptors. Journal of Neuroscience 26, 2956–2963.CrossRefGoogle ScholarPubMed

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Combined effect of genetic variants in the GluN2B coding gene (GRIN2B) on prefrontal function during working memory performance
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Combined effect of genetic variants in the GluN2B coding gene (GRIN2B) on prefrontal function during working memory performance
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