Glutamatergic gene variants impact the clinical profile of efficacy and side effects of haloperidol

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Glutamatergic gene variants impact the clinical profile of efficacy and side effects of haloperidol. / Giegling, Ina; Drago, Antonio; Dolžan, Vita; Plesničar, Blanka Kores; Schäfer, Martin; Hartmann, Annette M; Sander, Thomas; Toliat, Mohammad Reza; Möller, Hans-Jürgen; Stassen, Hans H; Rujescu, Dan; Serretti, Alessandro.

I: Pharmacogenetics and Genomics, Bind 21, Nr. 4, 04.2011, s. 206-16.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Giegling, I, Drago, A, Dolžan, V, Plesničar, BK, Schäfer, M, Hartmann, AM, Sander, T, Toliat, MR, Möller, H-J, Stassen, HH, Rujescu, D & Serretti, A 2011, 'Glutamatergic gene variants impact the clinical profile of efficacy and side effects of haloperidol', Pharmacogenetics and Genomics, bind 21, nr. 4, s. 206-16. https://doi.org/10.1097/FPC.0b013e32833efb18

APA

Giegling, I., Drago, A., Dolžan, V., Plesničar, B. K., Schäfer, M., Hartmann, A. M., Sander, T., Toliat, M. R., Möller, H-J., Stassen, H. H., Rujescu, D., & Serretti, A. (2011). Glutamatergic gene variants impact the clinical profile of efficacy and side effects of haloperidol. Pharmacogenetics and Genomics, 21(4), 206-16. https://doi.org/10.1097/FPC.0b013e32833efb18

CBE

Giegling I, Drago A, Dolžan V, Plesničar BK, Schäfer M, Hartmann AM, Sander T, Toliat MR, Möller H-J, Stassen HH, Rujescu D, Serretti A. 2011. Glutamatergic gene variants impact the clinical profile of efficacy and side effects of haloperidol. Pharmacogenetics and Genomics. 21(4):206-16. https://doi.org/10.1097/FPC.0b013e32833efb18

MLA

Vancouver

Giegling I, Drago A, Dolžan V, Plesničar BK, Schäfer M, Hartmann AM o.a. Glutamatergic gene variants impact the clinical profile of efficacy and side effects of haloperidol. Pharmacogenetics and Genomics. 2011 apr.;21(4):206-16. https://doi.org/10.1097/FPC.0b013e32833efb18

Author

Giegling, Ina ; Drago, Antonio ; Dolžan, Vita ; Plesničar, Blanka Kores ; Schäfer, Martin ; Hartmann, Annette M ; Sander, Thomas ; Toliat, Mohammad Reza ; Möller, Hans-Jürgen ; Stassen, Hans H ; Rujescu, Dan ; Serretti, Alessandro. / Glutamatergic gene variants impact the clinical profile of efficacy and side effects of haloperidol. I: Pharmacogenetics and Genomics. 2011 ; Bind 21, Nr. 4. s. 206-16.

Bibtex

@article{02cf10f09aea45bf97b2f9721b4133d7,
title = "Glutamatergic gene variants impact the clinical profile of efficacy and side effects of haloperidol",
abstract = "BACKGROUND: The glutamatergic system may be relevant to the pathophysiology of psychosis and to the effects of antipsychotic treatments.OBJECTIVES: We investigated a set of 62 SNPs located in genes coding for subunits of glutamatergic receptors (GAD1, GRIA1, GRIA3, GRIA4, GRID2, GRIK1, GRIK2, GRIK3, GRIK4, GRIN2B, GRM1 and GRM4), and the transporter of glycine (SLC6A5), as modulators of the effects of haloperidol.METHODS AND RESULTS: We studied a sample of 101 acutely ill psychotic patients. We then validated our result in two independent samples from Slovenia (n=71 and n=118) of schizophrenic patients treated with antipsychotics. We both investigated the antipsychotic effect (Positive and Negative Syndrome Scale) and motor side effect (Extrapyramidal Symptom Rating Scale) at baseline and days 3, 7, 14, 21 and 28. SLC6A5 variant (rs2298826) was found to be associated with a rapid rise of motor side effects at the beginning of the treatment (repeated measures of analysis of variance, P=0.0002), followed by a subsequent adaptation, probably dependent on haloperidol doses down titration. A specific effect was noted for dyskinetic symptoms. Haplotype analysis strengthened the relevance of SLC6A5: the C-A-C haplotype (rs1443548, rs883377, rs1945771) was found to be associated with higher Extrapyramidal symptom rating scale scores (overall P=0.01, haplotype P=0.000001). We successfully replicated this finding in the two independent samples from Slovenia.CONCLUSION: This result further stresses the relevance of the glutamatergic system in modulating the effects of haloperidol treatment, especially with regards to motor side effects.",
keywords = "Antipsychotic Agents, Genetic Variation, Genotype, Haloperidol, Haplotypes, Humans, Polymorphism, Single Nucleotide, Receptors, Glutamate, Slovenia",
author = "Ina Giegling and Antonio Drago and Vita Dol{\v z}an and Plesni{\v c}ar, {Blanka Kores} and Martin Sch{\"a}fer and Hartmann, {Annette M} and Thomas Sander and Toliat, {Mohammad Reza} and Hans-J{\"u}rgen M{\"o}ller and Stassen, {Hans H} and Dan Rujescu and Alessandro Serretti",
year = "2011",
month = apr,
doi = "10.1097/FPC.0b013e32833efb18",
language = "English",
volume = "21",
pages = "206--16",
journal = "Pharmacogenetics and Genomics",
issn = "1744-6872",
publisher = "LIPPINCOTT WILLIAMS & WILKINS",
number = "4",

}

RIS

TY - JOUR

T1 - Glutamatergic gene variants impact the clinical profile of efficacy and side effects of haloperidol

AU - Giegling, Ina

AU - Drago, Antonio

AU - Dolžan, Vita

AU - Plesničar, Blanka Kores

AU - Schäfer, Martin

AU - Hartmann, Annette M

AU - Sander, Thomas

AU - Toliat, Mohammad Reza

AU - Möller, Hans-Jürgen

AU - Stassen, Hans H

AU - Rujescu, Dan

AU - Serretti, Alessandro

PY - 2011/4

Y1 - 2011/4

N2 - BACKGROUND: The glutamatergic system may be relevant to the pathophysiology of psychosis and to the effects of antipsychotic treatments.OBJECTIVES: We investigated a set of 62 SNPs located in genes coding for subunits of glutamatergic receptors (GAD1, GRIA1, GRIA3, GRIA4, GRID2, GRIK1, GRIK2, GRIK3, GRIK4, GRIN2B, GRM1 and GRM4), and the transporter of glycine (SLC6A5), as modulators of the effects of haloperidol.METHODS AND RESULTS: We studied a sample of 101 acutely ill psychotic patients. We then validated our result in two independent samples from Slovenia (n=71 and n=118) of schizophrenic patients treated with antipsychotics. We both investigated the antipsychotic effect (Positive and Negative Syndrome Scale) and motor side effect (Extrapyramidal Symptom Rating Scale) at baseline and days 3, 7, 14, 21 and 28. SLC6A5 variant (rs2298826) was found to be associated with a rapid rise of motor side effects at the beginning of the treatment (repeated measures of analysis of variance, P=0.0002), followed by a subsequent adaptation, probably dependent on haloperidol doses down titration. A specific effect was noted for dyskinetic symptoms. Haplotype analysis strengthened the relevance of SLC6A5: the C-A-C haplotype (rs1443548, rs883377, rs1945771) was found to be associated with higher Extrapyramidal symptom rating scale scores (overall P=0.01, haplotype P=0.000001). We successfully replicated this finding in the two independent samples from Slovenia.CONCLUSION: This result further stresses the relevance of the glutamatergic system in modulating the effects of haloperidol treatment, especially with regards to motor side effects.

AB - BACKGROUND: The glutamatergic system may be relevant to the pathophysiology of psychosis and to the effects of antipsychotic treatments.OBJECTIVES: We investigated a set of 62 SNPs located in genes coding for subunits of glutamatergic receptors (GAD1, GRIA1, GRIA3, GRIA4, GRID2, GRIK1, GRIK2, GRIK3, GRIK4, GRIN2B, GRM1 and GRM4), and the transporter of glycine (SLC6A5), as modulators of the effects of haloperidol.METHODS AND RESULTS: We studied a sample of 101 acutely ill psychotic patients. We then validated our result in two independent samples from Slovenia (n=71 and n=118) of schizophrenic patients treated with antipsychotics. We both investigated the antipsychotic effect (Positive and Negative Syndrome Scale) and motor side effect (Extrapyramidal Symptom Rating Scale) at baseline and days 3, 7, 14, 21 and 28. SLC6A5 variant (rs2298826) was found to be associated with a rapid rise of motor side effects at the beginning of the treatment (repeated measures of analysis of variance, P=0.0002), followed by a subsequent adaptation, probably dependent on haloperidol doses down titration. A specific effect was noted for dyskinetic symptoms. Haplotype analysis strengthened the relevance of SLC6A5: the C-A-C haplotype (rs1443548, rs883377, rs1945771) was found to be associated with higher Extrapyramidal symptom rating scale scores (overall P=0.01, haplotype P=0.000001). We successfully replicated this finding in the two independent samples from Slovenia.CONCLUSION: This result further stresses the relevance of the glutamatergic system in modulating the effects of haloperidol treatment, especially with regards to motor side effects.

KW - Antipsychotic Agents

KW - Genetic Variation

KW - Genotype

KW - Haloperidol

KW - Haplotypes

KW - Humans

KW - Polymorphism, Single Nucleotide

KW - Receptors, Glutamate

KW - Slovenia

U2 - 10.1097/FPC.0b013e32833efb18

DO - 10.1097/FPC.0b013e32833efb18

M3 - Journal article

C2 - 20859245

VL - 21

SP - 206

EP - 216

JO - Pharmacogenetics and Genomics

JF - Pharmacogenetics and Genomics

SN - 1744-6872

IS - 4

ER -