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GWAS Antipsychotic Response

Jiang Li, Akane Yoshikawa, Mark D Brennan, Timothy L Ramsey, Herbert Y Meltzer
Biomarkers which predict response to atypical antipsychotic drugs (AAPDs) increases their benefit/risk ratio. We sought to identify common variants in genes which predict response to lurasidone, an AAPD, by associating genome-wide association study (GWAS) data and changes (Δ) in Positive And Negative Syndrome Scale (PANSS) scores from two 6-week randomized, placebo-controlled trials of lurasidone in schizophrenia (SCZ) patients. We also included SCZ risk SNPs identified by the Psychiatric Genomics Consortium using a polygenic risk analysis...
April 18, 2017: Schizophrenia Research
Ellen S Ovenden, Britt I Drögemöller, Lize van der Merwe, Bonginkosi Chiliza, Laila Asmal, Robin A Emsley, Louise Warnich
AIM: Noncoding variation has demonstrated regulatory effects on disease treatment outcomes. This study investigated the potential functionality of previously implicated noncoding variants on schizophrenia treatment response. MATERIALS & METHODS: Predicted regulatory potential of variation identified from antipsychotic response genome-wide association studies was determined. Prioritized variants were assessed for association(s) with treatment outcomes in a South African first episode schizophrenia cohort (n = 103)...
January 2017: Pharmacogenomics
Douglas M Ruderfer, Alexander W Charney, Ben Readhead, Brian A Kidd, Anna K Kähler, Paul J Kenny, Michael J Keiser, Jennifer L Moran, Christina M Hultman, Stuart A Scott, Patrick F Sullivan, Shaun M Purcell, Joel T Dudley, Pamela Sklar
BACKGROUND: Therapeutic treatments for schizophrenia do not alleviate symptoms for all patients and efficacy is limited by common, often severe, side-effects. Genetic studies of disease can identify novel drug targets, and drugs for which the mechanism has direct genetic support have increased likelihood of clinical success. Large-scale genetic studies of schizophrenia have increased the number of genes and gene sets associated with risk. We aimed to examine the overlap between schizophrenia risk loci and gene targets of a comprehensive set of medications to potentially inform and improve treatment of schizophrenia...
April 2016: Lancet Psychiatry
E Sacchetti, C Magri, A Minelli, P Valsecchi, M Traversa, S Calza, A Vita, M Gennarelli
The search for biomarkers of response to antipsychotic medications is hindered by difficulties inherent in the topic or related to persistent methodological difficulties, such as high rates of anticipated discontinuation and consequent distortions in the imputation of missing data. Because early response to antipsychotics represents a sufficiently reliable index of the subsequent treatment response in patients with schizophrenia, we undertook a real-world, genome-wide association study (GWAS) with the aim of identifying genetic predictors of response to risperidone after 2 weeks in 86 patients with schizophrenia...
March 2017: Pharmacogenomics Journal
Jian-Ping Zhang, Delbert G Robinson, Juan A Gallego, Majnu John, Jin Yu, Jean Addington, Mauricio Tohen, John M Kane, Anil K Malhotra, Todd Lencz
Findings from the Psychiatric Genomics Consortium genome-wide association study (GWAS) showed that variation at the DRD2 locus is associated with schizophrenia risk. However, the functional significance of rs2514218, the top DRD2 single nucleotide polymorphism in the GWAS, is unknown. Dopamine D2 receptor binding is a common mechanism of action for all antipsychotic drugs, and DRD2 variants were related to antipsychotic response in previous studies. The present study examined whether rs2514218 genotype could predict antipsychotic response, including efficacy and adverse events, in a cohort of patients with first episode of psychosis treated with either risperidone or aripiprazole for 12 weeks...
November 2015: Schizophrenia Bulletin
Eleanor Murphy, Francis J McMahon
An increasing focus on personalized medicine is driving a renewed effort to understand the impact of ethnic and genetic background on treatment outcomes. Since responses to psychopharmacological treatments continue to be sub-optimal, there is a pressing need to identify markers of tolerability and efficacy. Pharmacogenomic studies aim to find such markers within the human genome, and have made some progress in recent years. Progress has been slower in populations with diverse racial and ethnic backgrounds. Here we review 10 genome-wide association studies (GWAS) that assessed outcomes after antidepressant, antipsychotic, or mood stabilizer treatment...
September 2013: Discovery Medicine
Janusz K Rybakowski
Mood stabilizers form a cornerstone in the long-term treatment of bipolar disorder. The first representative of their family was lithium, still considered a prototype drug for the prevention of manic and depressive recurrences in bipolar disorder. Along with carbamazepine and valproates, lithium belongs to the first generation of mood stabilizers, which appeared in psychiatric treatment in the 1960s. Atypical antipsychotics with mood-stabilizing properties and lamotrigine, which were introduced in the mid-1990 s, form the second generation of such drugs...
March 2013: CNS Drugs
Shaunna L Clark, Renan P Souza, Daniel E Adkins, Karolina Aberg, József Bukszár, Joseph L McClay, Patrick F Sullivan, Edwin J C G van den Oord
OBJECTIVE: To examine the unique and congruent findings between multiple raters in a genome-wide association study (GWAS) in the context of understanding individual differences in treatment response during antipsychotic therapy for schizophrenia. MATERIALS AND METHODS: We performed GWAS to search for genetic variation affecting treatment response. The analysis sample included 738 patients with schizophrenia, successfully genotyped for ∼492k single nucleotide polymorphisms (SNPs) from the Clinical Antipsychotic Trial of Intervention Effectiveness...
February 2013: Pharmacogenetics and Genomics
Gavin P Reynolds
There is substantial interindividual variability in the effects of treatment with antipsychotic drugs not only in the emergence of adverse effects but also in symptom response. It is becoming increasingly clear that much of this variability is due to genetic factors; pharmacogenetics is the study of those factors, with the eventual goal of identifying genetic predictors of treatment effects. There have been many reported associations of single nucleotide polymorphisms (SNPs) in candidate genes with the consequences of antipsychotic drug treatment...
2012: Handbook of Experimental Pharmacology
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
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)...
August 2013: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Joseph L McClay, Daniel E Adkins, Karolina Aberg, Jozsef Bukszár, Amit N Khachane, Richard S E Keefe, Diana O Perkins, Joseph P McEvoy, T Scott Stroup, Robert E Vann, Patrick M Beardsley, Jeffrey A Lieberman, Patrick F Sullivan, Edwin J C G van den Oord
Neurocognitive deficits are a core feature of schizophrenia and, therefore, represent potentially critical outcome variables for assessing antipsychotic treatment response. We performed genome-wide association studies (GWAS) with 492K single nucleotide polymorphisms (SNPs) in a sample of 738 patients with schizophrenia from the Clinical Antipsychotic Trials of Intervention Effectiveness study. Outcome variables consisted of a neurocognitive battery administered at multiple time points over an 18-month period, measuring processing speed, verbal memory, vigilance, reasoning, and working memory domains...
February 2011: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
D E Adkins, K Aberg, J L McClay, J Bukszár, Z Zhao, P Jia, T S Stroup, D Perkins, J P McEvoy, J A Lieberman, P F Sullivan, E J C G van den Oord
Understanding individual differences in the susceptibility to metabolic side effects as a response to antipsychotic therapy is essential to optimize the treatment of schizophrenia. Here, we perform genomewide association studies (GWAS) to search for genetic variation affecting the susceptibility to metabolic side effects. The analysis sample consisted of 738 schizophrenia patients, successfully genotyped for 492K single nucleotide polymorphisms (SNPs), from the genomic subsample of the Clinical Antipsychotic Trial of Intervention Effectiveness study...
March 2011: Molecular Psychiatry
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