Pharmacogenomic overlap between antidepressant treatment response in major depression & antidepressant associated treatment emergent mania in bipolar disorder.

There is increasing interest in individualizing treatment selection for more than 25 regulatory approved treatments for major depressive disorder (MDD). Despite an inconclusive efficacy evidence base, antidepressants (ADs) are prescribed for the depressive phase of bipolar disorder (BD) with oftentimes, an inadequate treatment response and or clinical concern for mood destabilization. This study explored the relationship between antidepressant response in MDD and antidepressant-associated treatment emergent mania (TEM) in BD.

Antidepressant-Associated Treatment Emergent Mania: A Meta-Analysis to Guide Risk Modeling Pharmacogenomic Targets of Potential Clinical Value.

Background: The purpose of this study was to review the association between the SLC6A4 5-HTTLPR polymorphism and antidepressant (AD)-associated treatment emergent mania (TEM) in bipolar disorder alongside starting a discussion on the merits of developing risk stratification models to guide when not to provide AD treatment for bipolar depression.

Methods: Studies that examined the association between clinical and genetic risk factors, specifically monoaminergic transporter genetic variation, and TEM were identified. A meta-analysis was performed using the odds ratio to estimate the effect size under the Der-Simonian and Laird model.

Clinical characterization of patients with bipolar disorder and a history of asthma: An exploratory study.

Introduction: Bipolar disorder (BD) and asthma are leading causes of morbidity in the US and frequently co-occur.

Objectives: We evaluated the clinical features and comorbidities of patients with BD and a history of asthma.

Methods: In a cross-sectional analysis from the Mayo Clinic Bipolar Biobank, we explored the clinical characteristics of the BD and an asthma phenotype and fitted a multivariable regression model to identify risk factors for asthma.

Insulin resistance in bipolar disorder: A systematic review of illness course and clinical correlates.

Background: Although insulin resistance (IR) and cardiometabolic syndrome are prevalent in patients with bipolar disorder (BD), only a few studies have attempted to precisely assess the degree and clinical impact of IR in BD.

Methods: A comprehensive search was conducted from multiple research databases through May 2022, following a pre-defined protocol (PROSPERO: CRD42022359259). We extracted neuroimaging, cognition, illness course, and treatment response findings from individuals with BD with evidence of IR compared with euglycemic BD individuals.

Pharmacotherapy exposure as a marker of disease complexity in bipolar disorder: Associations with clinical & genetic risk factors.

Individuals with bipolar disorder (BD) require chronic pharmacotherapy, typically including medication switches or polypharmacy due to persisting symptoms or intolerable side effects. Here, we quantified pharmacotherapy exposure (PE) of Mayo Clinic BD Biobank participants using the number of cross-sectional (at enrollment) and lifetime BD-specific medications and medication classes, to understand the relationship between PE and markers of disease severity or treatment failure, psychiatric comorbidities, and polygenic risk scores (PRS) for six major psychiatric disorders. Being female (p < 0.

Polygenic prediction of bipolar disorder in a Latin American sample.

To date, bipolar disorder (BD) genetic studies and polygenic risk scores (PRSs) for BD are based primarily on populations of European descent (EUR) and lack representation from other ancestries including Latin American (LAT). Here, we describe a new LAT cohort from the Mayo Clinic Bipolar Biobank (MCBB), a multisite collaboration with recruitment sites in the United States (EUR; 1,443 cases and 777 controls) and Mexico and Chile (LAT; 211 cases and 161 controls) and use the sample to explore the performance of a BD-PRS in a LAT population. Using results from the largest genome-wide association study of BD in EUR individuals, PRSice2 and LDpred2 were used to compute BD-PRSs in the LAT and EUR samples from the MCBB.

Antidepressants that increase mitochondrial energetics may elevate risk of treatment-emergent mania.

Preclinical evidence suggests that antidepressants (ADs) may differentially influence mitochondrial energetics. This study was conducted to investigate the relationship between mitochondrial function and illness vulnerability in bipolar disorder (BD), specifically risk of treatment-emergent mania (TEM). Participants with BD already clinically phenotyped as TEM+ (n = 176) or TEM- (n = 516) were further classified whether the TEM associated AD, based on preclinical studies, increased (Mito+, n = 600) or decreased (Mito-, n = 289) mitochondrial electron transport chain (ETC) activity.

The genetics of bipolar disorder with obesity and type 2 diabetes.

Background: Bipolar disorder (BD) presents with high obesity and type 2 diabetes (T2D) and pathophysiological and phenomenological abnormalities shared with cardiometabolic disorders. Genomic studies may help define if they share genetic liability. This selective review of BD with obesity and T2D will focus on genomic studies, stress their current limitations and guide future steps in developing the field.

Quantification of diet quality utilizing the rapid eating assessment for participants-shortened version in bipolar disorder: Implications for prospective depression and cardiometabolic studies.

Objectives: Recognizing bipolar disorder as a multi-system metabolic condition driven, in part, by binge eating behavior and atypical depressive symptoms, this study aimed to quantify diet quality and evaluate clinical correlates in a bipolar disorder cohort.

Methods: Participants from the Mayo Clinic Bipolar Disorder Biobank (n = 734) completed the Rapid Eating Assessment for Participants - Shortened version (REAP-S) to determine diet quality. The average REAP-S score for a U.

Clinical Phenotype of Tardive Dyskinesia in Bipolar Disorder.

Purpose: Recognizing the negative impact that antipsychotic-induced movement disorders have on the quality of life and treatment outcomes in bipolar disorder (BD), this study aimed to assess clinical correlates and antipsychotic use patterns of tardive dyskinesia (TD+) in BD.

Materials And Methods: Participants with and without TD were included. Clinical variables were compared using t-test and χ2 test.

Association of Bipolar Disorder With Major Adverse Cardiovascular Events: A Population-Based Historical Cohort Study.

Objective: This study aimed to assess the association of bipolar disorder (BD) with risk of major adverse cardiac events (MACEs) after adjusting for established cardiovascular disease (CVD) risk factors.

Methods: We conducted a population-based historical cohort study using the Rochester Epidemiology Project. Patients older than 30 years with a clinical encounter from 1998 to 2000 with no prior MACE, atrial fibrillation, or heart failure were followed up through March 1, 2016.

Revisiting the bipolar disorder with migraine phenotype: Clinical features and comorbidity.

Introduction: To evaluate the prevalence and clinical correlates of lifetime migraine among patients with bipolar disorder (BD).

Methods: In a cross-sectional study, we evaluated 721 adults with BD from the Mayo Clinic Bipolar Disorder Biobank and compared clinical correlates of those with and without a lifetime history of migraine. A structured clinical interview (DSM-IV) and a clinician-assessed questionnaire were utilized to establish a BD diagnosis, lifetime history of migraine, and clinical correlates.

Pharmacogenetics in Psychiatry: Perceived Value and Opinions in a Chilean Sample of Practitioners.

Use of pharmacogenetics (PGx) testing to guide clinical decisions is growing in developed countries. Published guidelines for gene-drug pair analysis are available for prescriptions in psychiatry, but information on their utilization, barriers, and health outcomes in Latin America is limited. As a result, this work aimed at exploring current use, opinions, and perceived obstacles on PGx testing among psychiatrists in Chile, via an online, anonymous survey.

Body mass index and blood pressure in bipolar patients: Target cardiometabolic markers for clinical practice.

Objective: To evaluate the association between cardiometabolic markers and bipolar disorder (BD), examining the impact of sex and cardiometabolic medication use, from a large case-control biorepository of more than 1300 participants.

Patients And Methods: Recruited from July 2009 through September 2017, cardiometabolic markers were harvested from electronic health records (EHR) of participants (n=661) from the Mayo Clinic Individualized Medicine Biobank for Bipolar Disorder and Mayo Clinic Biobank age-sex-matched controls (n=706). Markers were compared between cases and controls using logistic regression, stratified by sex, adjusting for cardiometabolic medications and current smoking status.

Genome-wide Association Studies in Ancestrally Diverse Populations: Opportunities, Methods, Pitfalls, and Recommendations.

Genome-wide association studies (GWASs) have focused primarily on populations of European descent, but it is essential that diverse populations become better represented. Increasing diversity among study participants will advance our understanding of genetic architecture in all populations and ensure that genetic research is broadly applicable. To facilitate and promote research in multi-ancestry and admixed cohorts, we outline key methodological considerations and highlight opportunities, challenges, solutions, and areas in need of development.

Cytochrome P450 2C19 Poor Metabolizer Phenotype in Treatment Resistant Depression: Treatment and Diagnostic Implications.

Pharmacogenomic testing, specifically for pharmacokinetic (PK) and pharmacodynamic (PD) genetic variation, may contribute to a better understanding of baseline genetic differences in patients seeking treatment for depression, which may further impact clinical antidepressant treatment recommendations. This study evaluated PK and PD genetic variation and the clinical use of such testing in treatment seeking patients with bipolar disorder (BP) and major depressive disorder (MDD) and history of multiple drug failures/treatment resistance. Consecutive depressed patients evaluated at the Mayo Clinic Depression Center over a 10-year study time frame (2003-2013) were included in this retrospective analysis.

Association of schizophrenia polygenic risk score with manic and depressive psychosis in bipolar disorder.

Bipolar disorder (BD) is highly heterogeneous in symptomatology. Narrowing the clinical phenotype may increase the power to identify risk genes that contribute to particular BD subtypes. This study was designed to test the hypothesis that genetic overlap between schizophrenia (SZ) and BD is higher for BD with a history of manic psychosis.

Clinical features of bipolar spectrum with binge eating behaviour.

Objective: To determine whether bipolar spectrum disorder with binge eating behavior (BE) is an important clinical sub-phenotype.

Methods: Prevalence rates and correlates of different levels of BE were assessed in 1114 bipolar spectrum patients participating in a genetic biobank. BE and eating disorders (EDs) were assessed with the Eating Disorder Diagnostic Scale (EDDS).

Accumulating evidence for a role of TCF7L2 variants in bipolar disorder with elevated body mass index.

Objectives: Bipolar disorder (BD) is a complex disease associated with various hereditary traits, including a higher body mass index (BMI). In a prior genome-wide association study, we found that BMI modified the association of rs12772424 - a common variant in the gene encoding transcription factor 7-like 2 (TCF7L2) - with risk for BD. TCF7L2 is a transcription factor in the canonical Wnt pathway, involved in multiple disorders, including diabetes, cancer and psychiatric conditions.

Long-term risk of myocardial infarction and stroke in bipolar I disorder: A population-based Cohort Study.

Objectives: To estimate the risk of fatal and non-fatal myocardial infarction (MI) and stroke in patients with bipolar I disorder compared to people without bipolar I disorder.

Method: Utilizing a records-linkage system spanning 30 years (1966-1996), a population-based cohort of 334 subjects with bipolar I disorder and 334 age and sex-matched referents from Olmsted County, Minnesota, U.S.

Prevalence and correlates of DSM-5 eating disorders in patients with bipolar disorder.

Objective: To determine prevalence rates and clinical correlates of current DSM-5 eating disorders in patients with bipolar disorder (BP).

Methods: Prevalence rates of current DSM-5- and DSM-IV-defined binge eating disorder (BED), bulimia nervosa (BN), and anorexia nervosa (AN) were assessed with the Eating Disorder Diagnostic Scale (EDDS) in 1092 patients with BP. Psychiatric illness burden was evaluated with five proxy measures of BP illness severity.

Sex differences in the risk of rapid cycling and other indicators of adverse illness course in patients with bipolar I and II disorder.

Objectives: To examine the independent effects of sex on the risk of rapid cycling and other indicators of adverse illness course in patients with bipolar I disorder (BP-I) or bipolar II disorder (BP-II).

Methods: We analyzed data from the first 1,225 patients enrolled in the Mayo Clinic Individualized Medicine Biobank for Bipolar Disorder. Demographic and clinical variables were ascertained using standardized questionnaires; height and weight were assessed to determine body mass index (BMI).

Development of a bipolar disorder biobank: differential phenotyping for subsequent biomarker analyses.

Background: We aimed to establish a bipolar disorder biobank to serve as a resource for clinical and biomarker studies of disease risk and treatment response. Here, we describe the aims, design, infrastructure, and research uses of the biobank, along with demographics and clinical features of the first participants enrolled.

Methods: Patients were recruited for the Mayo Clinic Bipolar Biobank beginning in July 2009.

Association between history of psychosis and cardiovascular disease in bipolar disorder.

Objectives: To determine whether clinical features of bipolar disorder, such as history of psychosis, and cardiovascular disease (CVD) risk factors contribute to a higher risk of CVD among patients with bipolar disorder.

Methods: This cross-sectional study included a sample of 988 patients with bipolar I or bipolar II disorder or schizoaffective bipolar type confirmed by the Structured Clinical Interview for DSM-IV-TR disorders (SCID). Medical comorbidity burden was quantified utilizing the Cumulative Illness Severity Rating Scale (CIRS).