Risagerkara7401

The US Food and Drug Administration (FDA) recommends using only FDA-reviewed pharmacogenetic information to make prescribing decisions based on genetic test results. Such information is available in drug labeling and in the Table of Pharmacogenetic Associations ("Associations table").

To compile a list of drug-gene pairs from drug labeling and the Associations table and categorize the pharmacogenetic information and clinical outcome associated with each drug-gene pair.

This was a cross-sectional analysis of pharmacogenetic information in the Associations table and individual drug labeling in March 2020. We used the Table of Pharmacogenomic Biomarkers in Drug Labeling to identify drug labels to review. We categorized the pharmacogenetic information for each drug-gene pair according to whether the purpose was to describe (1) polymorphisms affecting drug disposition (metabolism or transport), (2) polymorphisms affecting a direct drug target, (3) variants associated with adverse drug reaction (ADR) susceptibility, (4) variants associated with therapeutic failure, (5) a biomarker-defined indication, or (6) a biomarker-defined ADR. We also categorized the clinical outcome-efficacy, safety, or unknown-associated with each drug-gene pair. We reported counts and proportions of drug-gene pairs in each pharmacogenetic information and clinical outcome category.

We identified 308 drug-gene pairs, of which 36% were associated with a biomarker-defined drug indication, 33% with polymorphic drug metabolism, and 28% with ADR susceptibility. Most drug-gene pairs (n = 267, 87%) were associated with an efficacy or safety-related outcome.

FDA-reviewed pharmacogenetic information is available for more than 300 drug-gene pairs and can help guide prescribing decisions.

FDA-reviewed pharmacogenetic information is available for more than 300 drug-gene pairs and can help guide prescribing decisions.

Certain copy number variants (CNVs) greatly increase the risk of autism. The authors conducted a genetics-first study to investigate whether heterogeneity in the clinical presentation of autism is underpinned by specific genotype-phenotype relationships.

This international study included 547 individuals (mean age, 12.3 years [SD=4.2], 54% male) who were ascertained on the basis of having a genetic diagnosis of a rare CNV associated with high risk of autism (82 16p11.2 deletion carriers, 50 16p11.2 duplication carriers, 370 22q11.2 deletion carriers, and 45 22q11.2 duplication carriers), as well as 2,027 individuals (mean age, 9.1 years [SD=4.9], 86% male) with autism of heterogeneous etiology. Assessments included the Autism Diagnostic Interview-Revised and IQ testing.

The four genetic variant groups differed in autism symptom severity, autism subdomain profile, and IQ profile. However, substantial variability was observed in phenotypic outcome in individual genetic variant groups (74%-97% of the variance, depending on the trait), whereas variability between groups was low (1%-21%, depending on the trait). CNV carriers who met autism criteria were compared with individuals with heterogeneous autism, and a range of profile differences were identified. When clinical cutoff scores were applied, 54% of individuals with one of the four CNVs who did not meet full autism diagnostic criteria had elevated levels of autistic traits.

Many CNV carriers do not meet full diagnostic criteria for autism but nevertheless meet clinical cutoffs for autistic traits. Although profile differences between variants were observed, there is considerable variability in clinical symptoms in the same variant.

Many CNV carriers do not meet full diagnostic criteria for autism but nevertheless meet clinical cutoffs for autistic traits. Although profile differences between variants were observed, there is considerable variability in clinical symptoms in the same variant.Recent progress in the identification of genes and genomic regions contributing to autism spectrum disorder (ASD) has had a broad impact on our understanding of the nature of genetic risk for a range of psychiatric disorders, on our understanding of ASD biology, and on defining the key challenges now facing the field in efforts to translate gene discovery into an actionable understanding of pathology. While these advances have not yet had a transformative impact on clinical practice, there is nonetheless cause for real optimism reliable lists of risk genes are large and growing rapidly; the identified encoded proteins have already begun to point to a relatively small number of areas of biology, where parallel advances in neuroscience and functional genomics are yielding profound insights; there is strong evidence pointing to mid-fetal prefrontal cortical development as one nexus of vulnerability for some of the largest-effect ASD risk genes; and there are multiple plausible paths forward toward rational therapeutics development that, while admittedly challenging, constitute fundamental departures from what was possible prior to the era of successful gene discovery.Obsessive-compulsive disorder (OCD) is a common, chronic, and oftentimes disabling disorder. The only established first-line treatments for OCD are exposure and response prevention, and serotonin reuptake inhibitor medications (SRIs). However, a subset of patients fails to respond to either modality, and few experience complete remission. Selleckchem Docetaxel Beyond SRI monotherapy, antipsychotic augmentation is the only medication approach for OCD with substantial empirical support. Our incomplete understanding of the neurobiology of OCD has hampered efforts to develop new treatments or enhance extant interventions. This review focuses on several promising areas of research that may help elucidate the pathophysiology of OCD and advance treatment. Multiple studies support a significant genetic contribution to OCD, but pinpointing the specific genetic determinants requires additional investigation. The preferential efficacy of SRIs in OCD has neither led to discovery of serotonergic abnormalities in OCD nor to development of new serotonergic medications for OCD. Several lines of preclinical and clinical evidence suggest dysfunction of the glutamatergic system in OCD, prompting testing of several promising glutamate modulating agents. Functional imaging studies in OCD show consistent evidence for increased activity in brain regions that form a cortico-striato-thalamo-cortical (CSTC) loop. Neuromodulation treatments with either noninvasive devices (e.g., transcranial magnetic stimulation) or invasive procedures (e.g., deep brain stimulation) provide further support for the CSTC model of OCD. A common substrate for various interventions (whether drug, behavioral, or device) may be modulation (at different nodes or connections) of the CSTC circuit that mediates the symptoms of OCD.