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Genome-wide association study of patient-rated and clinician-rated global impression of severity during antipsychotic treatment.

ABSTRACT: 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.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. Outcomes included both clinician and patient report of illness severity on global impression scales, the clinical global impression severity scale and patient global impression, respectively. Our criterion for genome-wide significance was a prespecified threshold ensuring that, on average, only 10% of the significant findings are false discoveries.Thirteen SNPs reached genome-wide significance. The top findings indicated three SNPs in PDE4D, 5q12.1 (P=4.2×10, 1.6×10, 1.8×10), mediating the effects of quetiapine on patient-reported severity and an additional three SNPs in TJP1, 15q13.1 (P=2.25×10, 4.86×10, 4.91×10), mediating the effects of risperidone on patient-reported severity. For clinician-reported severity, two SNPs in PPA2, 4q24 (P=3.68×10, 5.05×10), were found to reach genome-wide significance.We found evidence of both a novel and a consistent association when examining the results from the patient and clinician ratings, suggesting that different raters may capture unique facets of schizophrenia. Although our findings require replication and functional validation, this study shows the potential of GWAS to discover genes that potentially mediate treatment response of antipsychotic medication.

SUBMITTER: Clark SL

PROVIDER: S-EPMC3922978 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Genome-wide association study of patient-rated and clinician-rated global impression of severity during antipsychotic treatment.

Clark Shaunna L SL Souza Renan P RP Adkins Daniel E DE Aberg Karolina K Bukszár József J McClay Joseph L JL Sullivan Patrick F PF van den Oord Edwin J C G EJ

Pharmacogenetics and genomics 20130201 2

<h4>Objective</h4>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.<h4>Materials and methods</h4>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) fro ...[more]

PMID: 23241943

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Project description:Importance:Prior studies suggesting clinician fulfillment or denial of requests affects patient satisfaction included limited adjustment for patient confounders. The studies also did not examine distinct request types, yet patient expectations and clinician fulfillment or denial might vary among request types. Objective:To examine how patient satisfaction with the clinician is associated with clinician denial of distinct types of patient requests, adjusting for patient characteristics. Design, Setting, and Participants:Cross-sectional observational study of 1319 outpatient visits to family physicians (n = 56) by 1141 adults at one Northern California academic health center. Main Outcomes and Measures:We used 6 Consumer Assessment of Healthcare Providers and Systems Clinician and Group Adult Visit Survey items to measure patient satisfaction with the visit physician. Standardized items were averaged to form the satisfaction score (Cronbach α = 0.80), which was then percentile-transformed. Seven separate linear mixed-effects models examined the adjusted mean differences in patient satisfaction percentile associated with denial of each of the following requests (if present)-referral, pain medication, antibiotic, other new medication, laboratory test, radiology test, or other test-compared with fulfillment of the respective requests. The models adjusted for patient sociodemographics, weight, health status, personality, worry over health, prior visit with clinician, and the other 6 request categories and their dispositions. Results:The mean (SD) age of the 1141 patients was 45.6 (16.1) years, and 902 (68.4%) were female. Among 1319 visits, 897 (68.0%) included at least 1 request; 1441 (85.2%) were fulfilled. Requests by category were referral, 294 (21.1%); pain medication, 271 (20.5%); antibiotic, 107 (8.1%); other new medication, 271 (20.5%); laboratory test, 448 (34.0%); radiology test, 153 (11.6%); and other tests, 147 (11.1%). Compared with fulfillment of the respective request type, clinician denials of requests for referral, pain medication, other new medication, and laboratory test were associated with worse satisfaction (adjusted mean percentile differences, -19.75 [95% CI, -30.75 to -8.74], -10.72 [95% CI, -19.66 to -1.78], -20.36 [95% CI, -29.54 to -11.18], and -9.19 [95% CI, -17.50 to -0.87]), respectively. Conclusions and Relevance:Clinician denial of some types of requests was associated with worse patient satisfaction with the clinician, but not for others, when compared with fulfillment of the requests. In an era of patient satisfaction-driven compensation, the findings suggest the need to train clinicians to deal effectively with requests, potentially enhancing patient and clinician experiences.

Dataset Information

Genome-wide association study of patient-rated and clinician-rated global impression of severity during antipsychotic treatment.

Publications

Genome-wide association study of patient-rated and clinician-rated global impression of severity during antipsychotic treatment.

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