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Gene polymorphism influencing treatment response in psychotic patients in a naturalistic setting
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Division of Pharmacokinetics and Drug Therapy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.ORCID iD: 0000-0002-6368-2622
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology. (Farmakogenetik)
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2008 (English)In: Journal of Psychiatric Research, ISSN 0022-3956, E-ISSN 1879-1379, Vol. 42, no 11, 884-893 p.Article in journal (Refereed) Published
Abstract [en]

RATIONALE: Many patients with psychotic symptoms respond poorly to treatment. Factors possibly affecting treatment response include the presence of polymorphisms in genes coding for various receptor populations, drug-metabolizing enzymes or transport proteins. OBJECTIVES: To investigate whether genetic polymorphisms could be indicators of treatment response to antipsychotic drugs. The genes of interest were the dopamine D2 receptor gene (DRD2), the serotonin 2A and 2C receptor genes (HTR2A and HTR2C), the P-glycoprotein gene (ABCB1 or MDR1) and the drug-metabolizing cytochrome P450 2D6 gene (CYP2D6). MATERIAL AND METHODS: Data for this naturalistic, cross-sectional study of patients requiring antipsychotic drugs and attending the Psychosis Outpatient Care clinic in Jönköping, Sweden were obtained from patient interviews, blood samples and information from patient files. Blood samples were genotyped for DRD2 Taq1 A, Ins/Del and Ser311Cys, HTR2A T102C, HTR2C Cys23Ser, ABCB1 1236C>T, 2677G>T/A, 3435C>T and genetic variants of CYP2D6. The patients (n=116) were grouped according to the CANSEPT method regarding significant social and clinical needs and significant side effects. RESULTS: Patients on olanzapine homozygous for ABCB1 3435T, had more significant social and clinical needs than others. Patients with one or two DRD2 Taq1 A1 alleles had a greater risk of significant side effects, particularly if they were male, Caucasian, had a schizophrenic or delusional disorder or were taking strong dopamine D2-receptor antagonistic drugs. CONCLUSION: If these results are confirmed, patients carrying the DRD2 Taq1 A1 allele would benefit from using drugs without strong dopamine D2 receptor antagonistic properties.

Place, publisher, year, edition, pages
2008. Vol. 42, no 11, 884-893 p.
Keyword [en]
DRD2, 5-HT2, ABCB1, Cytochrome P-450 CYP2D6, Antipsychotic agents, Schizophrenia
National Category
Pharmaceutical Sciences Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-98079DOI: 10.1016/j.jpsychires.2007.10.007ISI: 000258798300002PubMedID: 18086475OAI: oai:DiVA.org:uu-98079DiVA: diva2:173254
Available from: 2009-02-11 Created: 2009-02-11 Last updated: 2017-12-13
In thesis
1. Treatment Response in Psychotic Patients in a Naturalistic Setting: Classification, Genes, Drugs, Insight and Social Networks
Open this publication in new window or tab >>Treatment Response in Psychotic Patients in a Naturalistic Setting: Classification, Genes, Drugs, Insight and Social Networks
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Many patients with psychotic symptoms respond poorly to treatment. Various approaches have been made to classify these patients according to treatment response. However, existing classifications have been criticized for various reasons and a new classification system is needed. Further, no satisfactory explanation of the poor treatment response has been apparent. The general aim of this thesis was therefore to develop and validate a new classification method of functional remission in a naturalistic population of patients with psychosis and to utilize this classification to investigate the population from genetic, drug treatment, insight and social network points of view.

Data for this cross-sectional study of patients (n=123) attending the Psychosis Outpatient Care clinic in the county of Jönköping, Sweden, were obtained from patient interviews, blood samples and information from patient files. The new classification method CANSEPT, which combines the CAN rating scale (CAN), the UKU side effect rating scale (SE) and the patient’s previous treatment history (PT), showed validity in discriminating the patients and was accepted well by the patients. CANSEPT was used to group the patients in the other studies in this thesis.

The results indicated that the gene polymorphism ABCB1 3435T, was related to worse significant social and clinical needs for patients on olanzapine, while the polymorphism DRD2 Taq1 A1 was related to a greater risk of significant side effects; especially if male, or taking strong dopamine D2-receptor antagonistic drugs. Drug treatment factors were also related to treatment response; longer duration of untreated prodromal and early psychosis was seen for patients with current significant social and clinical needs and non-adherence to treatment was associated with worse significant side effects. Worse treatment outcomes also appeared to be associated with smaller social network groups, worse insight into illness, poorer knowledge of warning signs and worse coping strategies.

In summary, CANSEPT was shown to be a useful valid, multidimensional tool for classification of treatment response. Gene polymorphisms, duration of untreated illness, non-adherence to treatment, social networks and knowledge should be taken into consideration when investigating inadequate treatment response.

Place, publisher, year, edition, pages
Uppsala: Acta Unversitatis Upsaliensis, 2009. 71 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 88
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:uu:diva-9558 (URN)978-91-554-7414-0 (ISBN)
Public defence
2009-03-20, B42, BMC, Husargatan 3, Uppsala, 13:00 (English)
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Available from: 2009-02-27 Created: 2009-02-11 Last updated: 2011-05-11Bibliographically approved

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