Dataset Information

The Progress and Pitfalls of Pharmacogenetics-Based Precision Medicine in Schizophrenia Spectrum Disorders: A Systematic Review and Meta-Analysis.

ABSTRACT: The inadequate efficacy and adverse effects of antipsychotics severely affect the recovery of patients with schizophrenia spectrum disorders (SSD). We report the evidence for associations between pharmacogenetic (PGx) variants and antipsychotics outcomes, including antipsychotic response, antipsychotic-induced weight/BMI gain, metabolic syndrome, antipsychotic-related prolactin levels, antipsychotic-induced tardive dyskinesia (TD), clozapine-induced agranulocytosis (CLA), and drug concentration level (pharmacokinetics) in SSD patients. Through an in-depth systematic search in 2010-2022, we identified 501 records. We included 29 meta-analyses constituting pooled data from 298 original studies over 69 PGx variants across 39 genes, 4 metabolizing phenotypes of CYP2D9, and 3 of CYP2C19. We observed weak unadjusted nominal significant (p < 0.05) additive effects of PGx variants of DRD1, DRD2, DRD3, HTR1A, HTR2A, HTR3A, and COMT (10 variants) on antipsychotic response; DRD2, HTR2C, BDNF, ADRA2A, ADRB3, GNB3, INSIG2, LEP, MC4R, and SNAP25 (14 variants) on weight gain; HTR2C (one variant) on metabolic syndrome; DRD2 (one variant) on prolactin levels; COMT and BDNF (two variants) on TD; HLA-DRB1 (one variant) on CLA; CYP2D6 (four phenotypes) and CYP2C19 (two phenotypes) on antipsychotics plasma levels. In the future, well-designed longitudinal naturalistic multi-center PGx studies are needed to validate the effectiveness of PGx variants in antipsychotic outcomes before establishing any reproducible PGx passport in clinical practice.

SUBMITTER: Teng Y

PROVIDER: S-EPMC10052041 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Progress and Pitfalls of Pharmacogenetics-Based Precision Medicine in Schizophrenia Spectrum Disorders: A Systematic Review and Meta-Analysis.

Teng Yuxin Y Sandhu Amrit A Liemburg Edith J EJ Naderi Elnaz E Alizadeh Behrooz Z BZ

Journal of personalized medicine 20230304 3

The inadequate efficacy and adverse effects of antipsychotics severely affect the recovery of patients with schizophrenia spectrum disorders (SSD). We report the evidence for associations between pharmacogenetic (PGx) variants and antipsychotics outcomes, including antipsychotic response, antipsychotic-induced weight/BMI gain, metabolic syndrome, antipsychotic-related prolactin levels, antipsychotic-induced tardive dyskinesia (TD), clozapine-induced agranulocytosis (CLA), and drug concentration ...[more]

PMID: 36983653

Similar Datasets

Project description:ImportanceSchizophrenia spectrum disorders (SSDs) and autism spectrum disorder (ASD) both feature social cognitive deficits; however, these disorders historically have been examined separately using a range of tests and subdomain focus and at different time points in the life span. Moving beyond diagnostic categories and characterizing social cognitive deficits can enhance understanding of shared pathways across these disorders.ObjectiveTo investigate how deficits in social cognitive domains diverge or overlap between SSDs and ASD based on the extant literature.Data sourcesLiterature searches were conducted in MEDLINE, PsycInfo, Embase, and Web of Science from database inception until July 26, 2020.Study selectionOriginal research articles were selected that reported performance-based measures of social cognition in both SSDs and ASD samples. Selected articles also had to be published in English and use International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, DSM-IV, or more recent diagnostic criteria.Data extraction and synthesisThis systematic review and meta-analysis was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology reporting guidelines, including data extraction and quality assessment using a modified version of the Newcastle-Ottawa Scale. Data were pooled using a random-effects model.Main outcomes and measuresEffect sizes were calculated as Hedges g (SSDs vs ASD). The primary outcomes were performance on emotion processing tasks, theory of mind (ToM) tasks, and the Reading the Mind in the Eyes Test (RMET) in SSDs compared with ASD. Meta-regressions were performed for age difference, publication year, quality assessment scores, and antipsychotic medication use.ResultsOf the 4175 screened articles, 36 studies directly comparing social cognitive performance in individuals with SSDs vs ASD were included in the qualitative analysis (n = 1212 for SSDs groups and n = 1109 for ASD groups), and 33 studies were included in the quantitative analyses (n = 1113 for SSDs groups and n = 1015 for ASD groups). Most study participants were male (number of studies [k] = 36, 72% [878 of 1212] in SSDs groups and 82% [907 of 1109] in ASD groups), and age (k = 35) was older in SSDs groups (mean [SD], 28.4 [9.5] years) than in ASD groups (mean [SD], 23.3 [7.6] years). Included studies highlighted the prevalence of small, male-predominant samples and a paucity of cross-disorder clinical measures. The meta-analyses revealed no statistically significant differences between SSDs and ASD on emotion processing measures (k = 15; g = 0.12 [95% CI, -0.07 to 0.30]; P = .21; I2 = 51.0%; 1 outlier excluded), ToM measures (k = 17; g = -0.01 [95% CI, -0.21 to 0.19]; P = .92; I2 = 56.5%; 1 outlier excluded), or the RMET (k = 13; g = 0.25 [95% CI, -0.04 to 0.53]; P = .10; I2 = 75.3%). However, SSDs vs ASD performance differences between studies were statistically significantly heterogeneous, which was only minimally explained by potential moderators.Conclusions and relevanceIn this analysis, similar levels of social cognitive impairment were present, on average, in individuals with SSDs and ASD. Cross-disorder studies of social cognition, including larger samples, consensus batteries, and consistent reporting of measures, as well as data across multiple levels of analysis, are needed to help identify subgroups within and across disorders that may be more homogeneous in etiology and treatment response.

Dataset Information

The Progress and Pitfalls of Pharmacogenetics-Based Precision Medicine in Schizophrenia Spectrum Disorders: A Systematic Review and Meta-Analysis.

Publications

The Progress and Pitfalls of Pharmacogenetics-Based Precision Medicine in Schizophrenia Spectrum Disorders: A Systematic Review and Meta-Analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets