AKAP13, CACNA1, GRIK4 and GRIA1 genetic variations may be associated with haloperidol efficacy during acute treatment

Antonio Drago, Ina Giegling, Martin Schäfer, Annette M. Hartmann, Marion Friedl, Bettina Konte, Hans Jürgen Möller, Diana De Ronchi, Hans H. Stassen, Alessandro Serretti, Dan Rujescu

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

We previously investigated a sample of psychotic patients acutely ill and acutely treated with haloperidol in the search for genetic predictors of response at PANSS scores during the first month of treatment. In the present work we extend the analysis to a wider panel of genetic variations including SNPs harbored by genes whose products are involved in molecular pathways consistent with the latest results of genome-wide association studies (GWAS) of antipsychotic efficacy. 96 Patients were investigated. The results were replicated in an independent sample of bipolar manic patients treated with antipsychotics (n tot=470, the sample was retrieved from the STEP-BD). Outcomes were the PANSS variation through time in the first sample, and changes of mania symptomatology at any two consecutive observations in the public available STEP-BD replication sample. A list of variations harbored by AKAP13, CACNA1, GRIK4 and GRIA1 were found to be significantly associated with outcome in both samples (different set of variations for each sample). Results did not survived multiple testing in the original sample but were replicated in both samples. This finding stresses the relevance of the glutamatergic system and regulatory molecular cascades in antipsychotic response. Nonetheless, the level of significance and the indirect and incomplete replication mandate cautiousness and further replication.

Original languageEnglish
Pages (from-to)887-894
Number of pages8
JournalEuropean Neuropsychopharmacology
Volume23
Issue number8
DOIs
Publication statusPublished - Aug 2013

Fingerprint

Haloperidol
Antipsychotic Agents
Genome-Wide Association Study
Bipolar Disorder
Single Nucleotide Polymorphism
Therapeutics
Genes

Keywords

  • Antipsychotic
  • Gene
  • Haloperidol
  • PANSS
  • Pharmacogenetics

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Pharmacology (medical)
  • Biological Psychiatry
  • Neurology
  • Pharmacology

Cite this

AKAP13, CACNA1, GRIK4 and GRIA1 genetic variations may be associated with haloperidol efficacy during acute treatment. / Drago, Antonio; Giegling, Ina; Schäfer, Martin; Hartmann, Annette M.; Friedl, Marion; Konte, Bettina; Möller, Hans Jürgen; De Ronchi, Diana; Stassen, Hans H.; Serretti, Alessandro; Rujescu, Dan.

In: European Neuropsychopharmacology, Vol. 23, No. 8, 08.2013, p. 887-894.

Research output: Contribution to journalArticle

Drago, A, Giegling, I, Schäfer, M, Hartmann, AM, Friedl, M, Konte, B, Möller, HJ, De Ronchi, D, Stassen, HH, Serretti, A & Rujescu, D 2013, 'AKAP13, CACNA1, GRIK4 and GRIA1 genetic variations may be associated with haloperidol efficacy during acute treatment', European Neuropsychopharmacology, vol. 23, no. 8, pp. 887-894. https://doi.org/10.1016/j.euroneuro.2012.08.013
Drago, Antonio ; Giegling, Ina ; Schäfer, Martin ; Hartmann, Annette M. ; Friedl, Marion ; Konte, Bettina ; Möller, Hans Jürgen ; De Ronchi, Diana ; Stassen, Hans H. ; Serretti, Alessandro ; Rujescu, Dan. / AKAP13, CACNA1, GRIK4 and GRIA1 genetic variations may be associated with haloperidol efficacy during acute treatment. In: European Neuropsychopharmacology. 2013 ; Vol. 23, No. 8. pp. 887-894.
@article{55e9a957d08a4c689b80a91bc6e19111,
title = "AKAP13, CACNA1, GRIK4 and GRIA1 genetic variations may be associated with haloperidol efficacy during acute treatment",
abstract = "We previously investigated a sample of psychotic patients acutely ill and acutely treated with haloperidol in the search for genetic predictors of response at PANSS scores during the first month of treatment. In the present work we extend the analysis to a wider panel of genetic variations including SNPs harbored by genes whose products are involved in molecular pathways consistent with the latest results of genome-wide association studies (GWAS) of antipsychotic efficacy. 96 Patients were investigated. The results were replicated in an independent sample of bipolar manic patients treated with antipsychotics (n tot=470, the sample was retrieved from the STEP-BD). Outcomes were the PANSS variation through time in the first sample, and changes of mania symptomatology at any two consecutive observations in the public available STEP-BD replication sample. A list of variations harbored by AKAP13, CACNA1, GRIK4 and GRIA1 were found to be significantly associated with outcome in both samples (different set of variations for each sample). Results did not survived multiple testing in the original sample but were replicated in both samples. This finding stresses the relevance of the glutamatergic system and regulatory molecular cascades in antipsychotic response. Nonetheless, the level of significance and the indirect and incomplete replication mandate cautiousness and further replication.",
keywords = "Antipsychotic, Gene, Haloperidol, PANSS, Pharmacogenetics",
author = "Antonio Drago and Ina Giegling and Martin Sch{\"a}fer and Hartmann, {Annette M.} and Marion Friedl and Bettina Konte and M{\"o}ller, {Hans J{\"u}rgen} and {De Ronchi}, Diana and Stassen, {Hans H.} and Alessandro Serretti and Dan Rujescu",
year = "2013",
month = "8",
doi = "10.1016/j.euroneuro.2012.08.013",
language = "English",
volume = "23",
pages = "887--894",
journal = "European Neuropsychopharmacology",
issn = "0924-977X",
publisher = "Elsevier Science B.V.",
number = "8",

}

TY - JOUR

T1 - AKAP13, CACNA1, GRIK4 and GRIA1 genetic variations may be associated with haloperidol efficacy during acute treatment

AU - Drago, Antonio

AU - Giegling, Ina

AU - Schäfer, Martin

AU - Hartmann, Annette M.

AU - Friedl, Marion

AU - Konte, Bettina

AU - Möller, Hans Jürgen

AU - De Ronchi, Diana

AU - Stassen, Hans H.

AU - Serretti, Alessandro

AU - Rujescu, Dan

PY - 2013/8

Y1 - 2013/8

N2 - We previously investigated a sample of psychotic patients acutely ill and acutely treated with haloperidol in the search for genetic predictors of response at PANSS scores during the first month of treatment. In the present work we extend the analysis to a wider panel of genetic variations including SNPs harbored by genes whose products are involved in molecular pathways consistent with the latest results of genome-wide association studies (GWAS) of antipsychotic efficacy. 96 Patients were investigated. The results were replicated in an independent sample of bipolar manic patients treated with antipsychotics (n tot=470, the sample was retrieved from the STEP-BD). Outcomes were the PANSS variation through time in the first sample, and changes of mania symptomatology at any two consecutive observations in the public available STEP-BD replication sample. A list of variations harbored by AKAP13, CACNA1, GRIK4 and GRIA1 were found to be significantly associated with outcome in both samples (different set of variations for each sample). Results did not survived multiple testing in the original sample but were replicated in both samples. This finding stresses the relevance of the glutamatergic system and regulatory molecular cascades in antipsychotic response. Nonetheless, the level of significance and the indirect and incomplete replication mandate cautiousness and further replication.

AB - We previously investigated a sample of psychotic patients acutely ill and acutely treated with haloperidol in the search for genetic predictors of response at PANSS scores during the first month of treatment. In the present work we extend the analysis to a wider panel of genetic variations including SNPs harbored by genes whose products are involved in molecular pathways consistent with the latest results of genome-wide association studies (GWAS) of antipsychotic efficacy. 96 Patients were investigated. The results were replicated in an independent sample of bipolar manic patients treated with antipsychotics (n tot=470, the sample was retrieved from the STEP-BD). Outcomes were the PANSS variation through time in the first sample, and changes of mania symptomatology at any two consecutive observations in the public available STEP-BD replication sample. A list of variations harbored by AKAP13, CACNA1, GRIK4 and GRIA1 were found to be significantly associated with outcome in both samples (different set of variations for each sample). Results did not survived multiple testing in the original sample but were replicated in both samples. This finding stresses the relevance of the glutamatergic system and regulatory molecular cascades in antipsychotic response. Nonetheless, the level of significance and the indirect and incomplete replication mandate cautiousness and further replication.

KW - Antipsychotic

KW - Gene

KW - Haloperidol

KW - PANSS

KW - Pharmacogenetics

UR - http://www.scopus.com/inward/record.url?scp=84881659776&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84881659776&partnerID=8YFLogxK

U2 - 10.1016/j.euroneuro.2012.08.013

DO - 10.1016/j.euroneuro.2012.08.013

M3 - Article

C2 - 22980146

AN - SCOPUS:84881659776

VL - 23

SP - 887

EP - 894

JO - European Neuropsychopharmacology

JF - European Neuropsychopharmacology

SN - 0924-977X

IS - 8

ER -