Genetic analysis of psychosis Biotypes: shared Ancestry-adjusted polygenic risk and unique genomic associations.

The Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) created psychosis Biotypes based on neurobiological measurements in a multi-ancestry sample. These Biotypes cut across DSM diagnoses of schizophrenia, schizoaffective disorder, and bipolar disorder with psychosis. Two recently developed post hoc ancestry adjustment methods of Polygenic Risk Scores (PRSs) generate Ancestry-Adjusted PRSs (AAPRSs), which allow for PRS analysis of multi-ancestry samples.

Genetic Analysis of Psychosis Biotypes: Shared Ancestry-Adjusted Polygenic Risk and Unique Genomic Associations.

The Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) created psychosis Biotypes based on neurobiological measurements in a multi-ancestry sample. These Biotypes cut across DSM diagnoses of schizophrenia, schizoaffective disorder and bipolar disorder with psychosis. Two recently developed ancestry adjustment methods of Polygenic Risk Scores (PRSs) generate Ancestry-Adjusted PRSs (AAPRSs), which allow for PRS analysis of multi-ancestry samples.

The Pharmacogenomics Global Research Network Implementation Working Group: global collaboration to advance pharmacogenetic implementation.

Pharmacogenetics promises to optimize treatment-related outcomes by informing optimal drug selection and dosing based on an individual's genotype in conjunction with other important clinical factors. Despite significant evidence of genetic associations with drug response, pharmacogenetic testing has not been widely implemented into clinical practice. Among the barriers to broad implementation are limited guidance for how to successfully integrate testing into clinical workflows and limited data on outcomes with pharmacogenetic implementation in clinical practice.

Dopamine Transporter and Gene Relationships with Attention-Deficit/Hyperactivity Disorder Treatment Response in the Methylphenidate and Atomoxetine Crossover Study.

Few biological or clinical predictors guide medication selection and/or dosing for attention-deficit/hyperactivity disorder (ADHD). Accumulating data suggest that genetic factors may contribute to clinically relevant pharmacodynamic (e.g.

Cerebello-Parietal Functional Connectivity in Amnestic Mild Cognitive Impairment.

The role of the cerebellum in amnestic mild cognitive impairment (aMCI), typically a prodromal stage of Alzheimer's disease, is not fully understood. We studied the lobule-specific cerebello-cerebral connectivity in 15 cognitively normal and 16 aMCI using resting-state functional MRI. Our analysis revealed weaker connectivity between the cognitive cerebellar lobules and parietal lobe in aMCI.

Evidence from comprehensive independent validation studies for smooth pursuit dysfunction as a sensorimotor biomarker for psychosis.

Smooth pursuit eye movements are considered a well-established and quantifiable biomarker of sensorimotor function in psychosis research. Identifying psychotic syndromes on an individual level based on neurobiological markers is limited by heterogeneity and requires comprehensive external validation to avoid overestimation of prediction models. Here, we studied quantifiable sensorimotor measures derived from smooth pursuit eye movements in a large sample of psychosis probands (N = 674) and healthy controls (N = 305) using multivariate pattern analysis.

Serotonin Transporter (SLC6A4) and FK506-Binding Protein 5 (FKBP5) Genotype and Methylation Relationships with Response to Meditation in Veterans with PTSD.

Meditation-based interventions are novel and effective non-pharmacologic treatments for veterans with PTSD. We examined relationships between treatment response, early life trauma exposure, DNA polymorphisms, and methylation in the serotonin transporter (SLC6A4) and FK506-binding protein 5 (FKBP5) genes. DNA samples and clinical outcomes were examined in 72 veterans with PTSD who received meditation-based therapy in two separate studies of mindfulness-based stress reduction (MBSR) and Transcendental Meditation (TM).

Ritual and Power in Medicine: Questioning Honor Walks in Organ Donation.

Honor walks are ceremonies that purportedly honor organ donors as they make their final journey from the ICU to the OR. In this paper, we draw on Ronald Grimes' work in ritual studies to examine honor walks as ceremonial rituals that display medico-technological power in a symbolic social drama (Grimes, 1982). We argue that while honor walks claim to honor organ donors, ceremonies cannot primarily honor donors, but can only honor donation itself.

Pharmacogenetics in Child and Adolescent Psychiatry: Background and Evidence-Based Clinical Applications.

The efficacy and tolerability of psychotropic medications can vary significantly among children and adolescents, and some of this variability relates to pharmacogenetic factors. Pharmacogenetics (PGx) in child and adolescent psychiatry can potentially improve treatment outcomes and minimize adverse drug reactions. This article reviews key pharmacokinetic and pharmacodynamic genes and principles of pharmacogenetic testing and discusses the evidence base for clinical decision-making concerning PGx testing.

Cognitive Function Remains Associated With Functional Impairment in Profound Dementia: Alzheimer Disease and Dementia With Lewy Bodies.

Background And Objectives: The Baylor Profound Mental Status Examination (BPMSE) was developed to assess cognitive function in the profound stage of dementia. The Clinical Dementia Rating (CDR) scale has been widely used in measuring functional performance in dementia. We aimed to determine whether cognitive function is related to overall functional impairment in profound dementia.

A systematic review of clozapine-associated inflammation and related monitoring.

Clozapine is an effective antipsychotic medication used for treatment-resistant schizophrenia. However, it is underutilized due to rigorous hematologic monitoring requirements and many adverse drug reactions. Publications have highlighted the occurrence of inflammatory reactions, some life-threatening, particularly during the early stages of clozapine treatment.

Intersection and Considerations for Patient-Centered Care, Patient Experience, and Medication Experience in Pharmacogenomics.

As healthcare continues to embrace the concept of person- and patient-centered care, pharmacogenomics, patient experience, and medication experience will continue to play an increasingly important role in care delivery. This review highlights the intersection between these concepts and provides considerations for patient-centered medication and pharmacogenomic experiences. Elements at the patient, provider, and system level can be considered in the discussion, supporting the use of pharmacogenomics, with components of the patient and medication experience contributing to the mitigation of barriers surrounding patient use and the valuation of pharmacogenomic testing.

Assessing pharmacogenomic literacy in China through validation of the Chinese version of the Minnesota Assessment of Pharmacogenomic Literacy.

Pharmacogenomics (PGx) implementation into clinical care is rapidly increasing in China. However, the extent to which the public understands PGx testing and important knowledge domains requiring patient education or counseling remains unclear. To address this, we created and validated the Chinese version of the Minnesota Assessment of Pharmacogenomic Literacy (MAPL-C ).

Genetic variations in idiopathic pulmonary fibrosis and patient response to pirfenidone.

Background: Genetic variations in Idiopathic Pulmonary Fibrosis (IPF) affect survival and outcomes. Current antifibrotic agents are managed based on the patient's reported side effects, although certain single nucleotide polymorphisms (SNPs) might alter treatment response and survival depending on the antifibrotic administered. This study investigated variations in response and outcomes to pirfenidone based on patients-specific genetic profiles.

Peripheral inflammatory subgroup differences in anterior Default Mode network and multiplex functional network topology are associated with cognition in psychosis.

Introduction: High-inflammation subgroups of patients with psychosis demonstrate cognitive deficits and neuroanatomical alterations. Systemic inflammation assessed using IL-6 and C-reactive protein may alter functional connectivity within and between resting-state networks, but the cognitive and clinical implications of these alterations remain unknown. We aim to determine the relationships of elevated peripheral inflammation subgroups with resting-state functional networks and cognition in psychosis spectrum disorders.

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A Genotypes and Serotonin Reuptake Inhibitor Antidepressants.

Serotonin reuptake inhibitor antidepressants, including selective serotonin reuptake inhibitors (SSRIs; i.e., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline), serotonin and norepinephrine reuptake inhibitors (i.

Characterization of childhood trauma, hippocampal mediation and Cannabis use in a large dataset of psychosis and non-psychosis individuals.

Background: Cannabis use (CA) and childhood trauma (CT) independently increase the risk of earlier psychosis onset; but their interaction in relation to psychosis risk and association with endocannabinoid-receptor rich brain regions, i.e. the hippocampus (HP), remains unclear.

Peripheral inflammation is associated with impairments of inhibitory behavioral control and visual sensorimotor function in psychotic disorders.

Elevated markers of peripheral inflammation are common in psychosis spectrum disorders and have been associated with brain anatomy, pathology, and physiology as well as clinical outcomes. Preliminary evidence suggests a link between inflammatory cytokines and C-reactive protein (CRP) with generalized cognitive impairments in a subgroup of individuals with psychosis. Whether these patients with elevated peripheral inflammation demonstrate deficits in specific cognitive domains remains unclear.

Radiomic features of gray matter in never-treated first-episode schizophrenia.

Alterations of radiomic features (RFs) in gray matter are observed in schizophrenia, of which the results may be limited by small study samples and confounding effects of drug therapies. We tested for RFs alterations of gray matter in never-treated first-episode schizophrenia (NT-FES) patients and examined their associations with known gene expression profiles. RFs were examined in the first sample with 197 NT-FES and 178 healthy controls (HCs) and validated in the second independent sample (90 NT-FES and 74 HCs).

Disrupted subcortical functional connectome gradient in drug-naïve first-episode schizophrenia and the normalization effects after antipsychotic treatment.

Antipsychotics are thought to improve schizophrenia symptoms through the antagonism of dopamine D2 receptors, which are abundant mainly in subcortical regions. By introducing functional gradient, a novel approach to identify hierarchy alterations by capturing the similarity of whole brain fucntional connectivity (FC) profiles between two voxels, the present study aimed to characterize how the subcortical gradient is associated with treatment effects and response in first-episode schizophrenia in vivo. Two independent samples of first-episode schizophrenia (FES) patients with matched healthy controls (HC) were obtained: the discovery dataset included 71 patients (FES) and 64 HC at baseline, and patients were re-scanned after either 6 weeks (FES N = 33) or 12 months (FES N = 57) of antipsychotic treatment, of which 19 patients finished both 6-week and 12-month evaluation.

Public Attitudes toward Pharmacogenomic Testing and Establishing a Statewide Pharmacogenomics Database in the State of Minnesota.

The clinical adoption and implementation of pharmacogenomics (PGx) beyond academic medical centers remains slow, restricting the general population from benefitting from this important component of personalized medicine. As an initial step in the statewide initiative of PGx implementation in Minnesota, we engaged community members and assessed attitudes towards PGx testing and acceptability of establishing a secure statewide PGx database for clinical and research use among Minnesota residents. Data was collected from 808 adult attendees at the 2021 Minnesota State Fair through an electronic survey.