Acute antipyschotic efficacy and side effects in schizophrenia: Association with serotonin transporter promoter genotypes

Dolžan, Vita; Serretti, Alessandro; Mandelli, Laura; Koprivsek, Jure; Kastelic, Matej; Plesničar, Blanka Kores

doi:10.1016/j.pnpbp.2008.05.022

Cited by 45 publications

(38 citation statements)

References 47 publications

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“…5-HTTLPR Short-allele was demonstrated to be associated with poorer treatment response Dolzan et al, 95 Arranz et al, 96 Vazquez-Bourgon et al 97 …”

Section: -Httmentioning

confidence: 99%

“…In the gene encoding solute carrier family 6 (neurotransmitter transporter), member 4 (SLC6A4, synonymous with 5-HTT) 5-HT transporters, which terminate 5-HT action by transporting it back into the presynaptic neuron, an association of the short allele of the 44-bp ins/del polymorphism serotonin-transporterlinked polymorphic region (commonly referred to as 5-HTTLPR) with poorer AP response has consistently been demonstrated. [95][96][97] Further association with AP treatment response has been described for the G allele of -1019C/G SNP in 5-HT receptor 1A, G protein-coupled (HTR1A), encoding 5-HT 1A receptors, 98,99 for polymorphisms in the genes encoding subtypes 3A, B, and E of 5-HT 3 receptors 100,101 and for the 267C/T SNP in the gene encoding 5-HT 6 receptors. 102,103 However, this last finding has not been confirmed in all studies.…”

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confidence: 99%

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Pharmacogenetics of Antipsychotics

2014

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Objective: During the past decades, increasing efforts have been invested in studies to unravel the influence of genetic factors on antipsychotic (AP) dosage, treatment response, and occurrence of adverse effects. These studies aimed to improve clinical care by predicting outcome of treatment with APs and thus allowing for individualized treatment strategies. We highlight most important findings obtained through both candidate gene and genome-wide association studies, including pharmacokinetic and pharmacodynamic factors. Methods:We reviewed studies on pharmacogenetics of AP response and adverse effects published on PubMed until early 2012. Owing to the high number of published studies, we focused our review on findings that have been replicated in independent studies or are supported by meta-analyses.Results: Most robust findings were reported for associations between polymorphisms of the cytochrome P450 system, the dopamine and the serotonin transmitter systems, and dosage, treatment response, and adverse effects, such as AP-induced weight gain or tardive dyskinesia. These associations were either detected for specific medications or for classes of APs. Conclusion:First promising and robust results show that pharmacogenetics bear promise for a widespread use in future clinical practice. This will likely be achieved by developing algorithms that will include many genetic variants. However, further investigation is warranted to replicate and validate previous findings, as well as to identify new genetic variants involved in AP response and for replication of existing findings. W W W La pharmacogénétique des antipsychotiquesObjectif : Au cours des dernières décennies, des efforts croissants ont été déployés dans des études visant à percer l'influence des facteurs génétiques sur le dosage des antipsychotiques (AP), la réponse au traitement, et la survenue d'effets indésirables. Ces études voulaient améliorer les soins cliniques en prédisant le résultat du traitement par AP, et en donnant lieu ainsi à des stratégies de traitement individualisées. Nous présentons les résultats les plus importants obtenus par des études tant de gènes candidats que d'association pangénomique, notamment les facteurs pharmacocinétiques et pharmacodynamiques. Méthodes :Nous avons passé en revue les études sur la pharmacogénétique de la réponse aux AP et des effets indésirables publiées dans PubMed jusqu'au début de 2012. Vu le nombre élevé d'études publiées, notre revue a mis l'accent sur les résultats qui ont été reproduits dans des études indépendantes ou qui sont soutenus par des méta-analyses.

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“…5-HTTLPR Short-allele was demonstrated to be associated with poorer treatment response Dolzan et al, 95 Arranz et al, 96 Vazquez-Bourgon et al 97 …”

Section: -Httmentioning

confidence: 99%

mentioning

confidence: 99%

Pharmacogenetics of Antipsychotics

2014

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“…As a result, serotonin is recycled in a sodium-dependent method [20]. In three studies, one with a sample composed of 200 Caucasian participants [25], one with a sample of 129 Chinese participants [26] and one with a sample of 56 Caucasian participants [27], a deficient response was associated with the short allele for the 5-HTTLPR polymorphism for Clozapine and Risperidone treatment (Table 1). Again, there are different allele frequencies of the 5-HTTLPR polymorphism among the Africa American (22%), Caucasian (8.9%) and Asia (13%) populations.…”

Section: Httmentioning

confidence: 99%

The Impact of Drug and Gene Interaction on the Antipsychotic Medication for Schizophrenia

Cho¹,

Contreras²,

Garza³

et al. 2017

Bipolar Disord

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Objective: Schizophrenia, a neuropsychiatric disorder, is known to be neurodevelopmentally progressive. Due to the extensive interindividual variability found in the responses of patients, management of schizophrenia has proven to be challenging. This interindividual variability to treatment could be justified by the variation of the enzymes in charge of metabolizing medications, especially those associated with cytochrome P450. Since genetic factors influence the phenotypic responses to drugs, researchers are involved in identifying schizophrenic genetic factors, which could impact responses and severe effects for commonly known neuroleptic drugs known as pharmacogenetics. In order to predict drug response at the personal level, genetic variants that determine drug effects need to be identified. Methods:We have chosen to investigate gene targets for risperidone and clozapine, two commonly administered drugs for the treatment of schizophrenia. The aim of this review is to contribute in the understanding of genetic influences on drug responses of risperidone and clozapine in schizophrenia. We reviewed original primary research articles, meta-analysis, and review publications on drug and gene interaction on the treatment of schizophrenia. Our main findings focused on schizophrenia, pharmacogenetics and cytochrome P450. Results and conclusion:After filtering our results to human species and English language, a total of 45 scientific articles were used for this review. A promising direction for future research in schizophrenia treatment lies behind the identification of the specific genetic contributors that affect drug response.

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“…Data of the replication sample were previously reported in a pharmacogenetic study [24]. Seventy-one psychotic patients were enrolled in the Department of Psychiatry Teaching Hospital Maribor, affected by schizophrenia or schizoaffective disorders according to the DSM-IV-TR criteria.…”

Section: Replication Samplementioning

confidence: 99%

Early Antipsychotic Response Predictors in Schizophrenia: A Naturalistic Study

Porcelli¹

2014

JPCPY

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Studies on schizophrenia failed to find predictors of antipsychotic response, early response apart. We therefore hypothesized that early responders (ERs) could be identified by specific clinical characteristics. Two independent samples of schizophrenic patients were analyzed. Further, analyses were repeated merging the two samples (total=171). Factors associated with early response were also analyzed in patients taking first and second generation antipsychotics (FGAs and SGAs). A t test or a wilcoxon test was used to detect significant differences between ERs and early non responders (ENRs). In the investigation sample ERs had a lower illness duration (p=0.02), suffered from more severe positive (p=0.01), general (p=0.01) and hostile avoidance, that is represented by impulsivity, excitement, hostility and uncooperativeness, (p=0.01); these results were substantially confirmed in the replication sample and in the two samples merged. Results obtained in FGAs-treated patients were similar to those observed in the whole sample. In patients taking SGAs, ERs had more severe positive and depressive symptoms, without differences among other factors. In line with previous findings, the most relevant difference between ERs and ENRs was in the age, ERs being with a natural tendency younger (mean age ERs=39.6, ENRs=49.5). Regarding FGAs/SGAs differences, our results suggest that in ENRs treated with FGAs an increase of antipsychotic drug dosage seems to be of scarce benefit. Switching to a SGA might be of more clinical usefulness.

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Acute antipyschotic efficacy and side effects in schizophrenia: Association with serotonin transporter promoter genotypes

Cited by 45 publications

References 47 publications

Pharmacogenetics of Antipsychotics

Pharmacogenetics of Antipsychotics

The Impact of Drug and Gene Interaction on the Antipsychotic Medication for Schizophrenia

Early Antipsychotic Response Predictors in Schizophrenia: A Naturalistic Study

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