N-methyl-d-aspartate receptor NR2B subunit gene GRIN2B in schizophrenia and bipolar disorder: Polymorphisms and mRNA levels

Martucci, Livia; Wong, Albert H.C.; Luca, Vincenzo De; Likhodi, Olga; Wong, Greg; King, Nicole; Kennedy, James L.

doi:10.1016/j.schres.2006.02.001

Cited by 118 publications

(84 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In this regard lamotrigine, which is preferred for treating bipolar depression and rapid recycling, is considered to act in part by reducing presynaptic glutamate release [22]. A role for both receptor subtypes is consistent with evidence of disturbed dopaminergic and NMDA transmission in bipolar disorder [1,13,20,28,31,36,37,40].…”

Section: Discussionmentioning

confidence: 93%

Chronic Carbamazepine Administration Attenuates Dopamine D2-like Receptor-Initiated Signaling via Arachidonic Acid in Rat Brain

et al. 2008

View full text Add to dashboard Cite

Observations that dopaminergic antagonists are beneficial in bipolar disorder and that dopaminergic agonists can produce mania suggest that bipolar disorder involves excessive dopaminergic transmission. Thus, mood stabilizers used to treat the disease might act in part by downregulating dopaminergic transmission. In agreement, we reported that dopamine D 2 -like receptor mediated signaling involving arachidonic acid (AA, 20:4n-6) was downregulated in rats chronically treated with lithium. To see whether chronic carbamazepine, another mood stabilizer, did this as well, we injected i.p. saline or the D 2 -like receptor agonist, quinpirole (1 mg/kg), into unanesthetized rats that had been pretreated for 30 days with i.p. carbamazepine (25 mg/kg/day) or vehicle, and used quantitative autoradiography to measure regional brain incorporation coefficients (k*) for AA, markers of signaling. We also measured brain prostaglandin E 2 (PGE 2 ), an AA metabolite. In vehicle-treated rats, quinpirole compared with saline significantly increased k* for AA in 35 of 82 brain regions examined, as well as brain PGE 2 concentration. Affected regions belong to dopaminergic circuits and have high D 2 -like receptor densities. Chronic carbamazepine pretreatment prevented the quinpirole-induced increments in k* and in PGE 2 . These findings are consistent with the hypothesis that effective mood stabilizers generally downregulate brain AA signaling via D 2 -like receptors, and that this signaling is upregulated in bipolar disorder.

show abstract

Section: Discussionmentioning

confidence: 93%

Chronic Carbamazepine Administration Attenuates Dopamine D2-like Receptor-Initiated Signaling via Arachidonic Acid in Rat Brain

et al. 2008

View full text Add to dashboard Cite

show abstract

“…As such, the study focused on the overall mRNA level, not on variants. 34,35 In total, 57 SZ risk genes overlapped with our differential expression gene list findings from whole genome screening of thalamic neurons in postmortem schizophrenic brains. Among these, only 25 genes were reported for at least one positive SNP finding in all association studies (Supplementary Table 2).…”

Section: Discussionmentioning

confidence: 93%

An integrated genomic analysis of gene-function correlation on schizophrenia susceptibility genes

Chu

Liu

2010

J Hum Genet

View full text Add to dashboard Cite

Schizophrenia is a highly complex inheritable disease characterized by numerous genetic susceptibility elements, each contributing a modest increase in risk for the disease. Although numerous linkage or association studies have identified a large set of schizophrenia-associated loci, many are controversial. In addition, only a small portion of these loci overlaps with the large cumulative pool of genes that have shown changes of expression in schizophrenia. Here, we applied a genomic gene-function approach to identify susceptibility loci that show direct effect on gene expression, leading to functional abnormalities in schizophrenia. We carried out an integrated analysis by cross-examination of the literature-based susceptibility loci with the schizophrenia-associated expression gene list obtained from our previous microarray study (Journal of Human Genetics (2009) 54: 665-75) using bioinformatic tools, followed by confirmation of gene expression changes using qPCR. We found nine genes (CHGB, SLC18A2, SLC25A27, ESD, C4A/C4B, TCP1, CHL1 and CTNNA2) demonstrate gene-function correlation involving: synapse and neurotransmission; energy metabolism and defense mechanisms; and molecular chaperone and cytoskeleton. Our findings further support the roles of these genes in genetic influence and functional consequences on the development of schizophrenia. It is interesting to note that four of the nine genes are located on chromosome 6, suggesting a special chromosomal vulnerability in schizophrenia.

show abstract

“…The GRIN2B gene is mainly expressed in forebrain structures such as the hippocampus, striatum, thalamus and olfactory bulb [17]. Its altered expression at the protein level has been observed in bipolar disorder [16]; however, it was not confirmed by a recent study by Martucci et al [9].…”

Section: Introductionmentioning

confidence: 89%

“…The three GRIN2B polymorphisms, 366C/G (Pro122) (rs7301328), rs890G/T and -200T/G (rs1019358), were analyzed by PCR-RFLP analysis according to Ohtsuki et al [13], with minor modifications. The SNP selection was based on the functionality of the -200G/T polymorphism [9,11] and the fact that the other two polymorphisms (rs7301328 and rs890) showed positive association with schizophrenia [1,13], which may have some common genetic background with bipolar disorder.…”

Section: Subjectsmentioning

confidence: 99%

No association of three GRIN2B polymorphisms with lithium response in bipolar patients

Szczepankiewicz

Skibińska

Suwalska

et al. 2009

Pharmacological Reports

View full text Add to dashboard Cite

Abstract:We investigated three polymorphisms in the NMDA receptor 2B subunit gene (GRIN2B) as a candidate gene for lithium response involved in glutamatergic neurotransmission. One hundred five bipolar patients treated with lithium for at least 5 years were analyzed. The lithium response was assessed as excellent -no affective episodes during lithium treatment; partial -50% reduction in the episode index; or no response -less than 50% reduction, no change or worsening in the episode index. Genotypes for the -200G/T, 366C/G and rs890G/T GRIN2B polymorphisms were established using the PCR-RFLP method. Genotype distributions were in Hardy-Weinberg equilibrium for all three polymorphisms. No association was found between the three polymorphisms studied and the treatment response to lithium. The authors conclude that polymorphisms of the GRIN2B gene did not show an association with the treatment response to lithium in bipolar patients.

show abstract

N-methyl-d-aspartate receptor NR2B subunit gene GRIN2B in schizophrenia and bipolar disorder: Polymorphisms and mRNA levels

Cited by 118 publications

References 44 publications

Chronic Carbamazepine Administration Attenuates Dopamine D2-like Receptor-Initiated Signaling via Arachidonic Acid in Rat Brain

Chronic Carbamazepine Administration Attenuates Dopamine D2-like Receptor-Initiated Signaling via Arachidonic Acid in Rat Brain

An integrated genomic analysis of gene-function correlation on schizophrenia susceptibility genes

No association of three GRIN2B polymorphisms with lithium response in bipolar patients

Contact Info

Product

Resources

About