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 language | English |
|---|---|
| Pages (from-to) | 887-894 |
| Number of pages | 8 |
| Journal | European Neuropsychopharmacology |
| Volume | 23 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Aug 2013 |
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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 journal › Article
}
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 -