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April 2007 - present
Publications
Publications (62)
Psychiatric disorders are highly heritable and polygenic, influenced by environmental factors and often comorbid. Large-scale genome-wide association studies (GWASs) through consortium efforts have identified genetic risk loci and revealed the underlying biology of psychiatric disorders and traits. However, over 85% of psychiatric GWAS participants...
Bipolar disorder is a chronic and complex polygenic disease with high rates of comorbidity. However, the independent contribution of either diagnosis or genetic risk of bipolar disorder to the medical comorbidity profile of individuals with the disease remains unresolved. Here, we conducted a multi-step phenome-wide association study (PheWAS) of bi...
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 clini...
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....
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 with oftentimes an inadequate treatment response and or clinical co...
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...
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...
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 s...
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...
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 pheno...
Introduction
Patients with bipolar disorder (BD) have an increased risk for cardiovascular morbimortality. Clinical risk factors, specifically for arrhythmias and sudden cardiac death remain understudied.
Objectives
This study was conducted to assess differences in cardiac conduction among BD patients.
Methods
We included patients with BD in a cr...
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...
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...
Background
Bipolar disorder (BD) with co-occurring attention deficit-hyperactivity disorder (ADHD) is associated with an unfavorable course of illness. We aimed to identify potential clinical and genetic correlates of BD with and without ADHD.
Methods
Among patients with BD (N = 2,198) enrolled in the Mayo Clinic Bipolar Biobank we identified thos...
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....
Objective:
To assess the association of bipolar disorder (BD) with risk of major adverse cardiac events (MACE) after adjusting for established cardiovascular disease (CVD) risk factors.
Patients and methods:
We conducted a population-based historical cohort study using the Rochester Epidemiology Project. Patients aged >30 with a clinical encount...
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...
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, o...
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 fro...
Background:
Treatment in bipolar disorder (BD) is commonly applied as a multimodal therapy based on decision algorithms that lack an integrative understanding of molecular mechanisms or a biomarker associated clinical outcome measure. Pharmacogenetics/genomics study the individual genetic variation associated with drug response. This selective rev...
Objectives
The association of bipolar disorder with early and excessive cardiovascular disease was identified over a century ago. Nonetheless, the vascular‐bipolar link remains under‐recognized, particularly with regard to how this link can contribute to our understanding of pathogenesis and treatment.
Methods
An international group of experts com...
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...
Background: 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 genet...
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. Analyses...
Methods:
This national register study of 10 631 817 people in Sweden included 46 911 people who were admitted to the hospital for schizophrenia between 1 January 1987 and 31 December 2010. Information from national registers was used to identify people who had schizophrenia and obtain data about mortality, causes of death, medical diagnoses and ho...
Patients with bipolar disorder (BD) have a high prevalence of comorbid medical illness. However, the mechanisms underlying these comorbidities with BD are not well known. Certain genetic variants may have pleiotropic effects, increasing the risk of BD and other medical illnesses simultaneously. In this study, we evaluated the association of BD-susc...
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 Disord...
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...
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 re...
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.
Patients were recruited for the May...
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 10...
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. Demographi...
Acamprosate has been widely used since the Food and Drug Administration approved the medication for treatment of alcohol use disorders (AUDs) in 2004. Although the detailed molecular mechanism of acamprosate remains unclear, it has been largely known that acamprosate inhibits glutamate action in the brain. However, AUD is a complex and heterogeneou...
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.
This cross-sectional study included a sample of 988 patients with bipolar I or bipolar II disorder or schizoaffective bipolar type confirmed...
Purinergic signaling regulates numerous vital biological processes in the central nervous system (CNS). The two principle purines, ATP and adenosine act as excitatory and inhibitory neurotransmitters, respectively. Compared to other classical neurotransmitters, the role of purinergic signaling in psychiatric disorders is not well understood or appr...
Identifying clinical and genetic risk factors associated with antidepressant-induced mania (AIM) may improve individualized treatment strategies for bipolar depression.
From 2009 to 2012, bipolar depressed patients, confirmed by DSM-IV-TR-structured interview, were screened for AIM. An AIM+ case was defined as a manic/hypomanic episode within 60 da...
Depression is the predominant pole of illness disability in bipolar disorder and, compared with acute mania, has less systematic research guiding treatment development. The aim of this review is to present the therapeutic options currently available for managing bipolar depression and to highlight areas of unmet need and future research.
Literature...
Intracerebroventricular administration of neurotensin (NT) suppresses locomotor activity. However, the brain regions that mediate the locomotor depressant effect of NT and receptor subtype-specific mechanisms involved are unclear. Using a brain-penetrating, selective NT receptor type 1 (NTS1) agonist PD149163, we investigated the effect of systemic...
Objective
To review the evidence on and estimate the risk of myocardial infarction and stroke in bipolar disorder.MethodA systematic search using MEDLINE, EMBASE, PsycINFO, Web of Science, Scopus, Cochrane Database of Systematic Reviews, and bibliographies (1946 – May, 2013) was conducted. Case-control and cohort studies of bipolar disorder patient...
Introduction: In bipolar disorder (BD) successive episodes worsen the prognosis. Thus, maintenance therapy to prevent recurrence is a cornerstone of the therapeutic approach. Method: Review of the relevant literature on maintenance treatment of BD.
Results: The majority of maintenance treatment studies have used designs enriched. The- se designs li...
Background:
To explore the relationship between binge eating disorder (BED) and obesity in patients with bipolar disorder (BP).
Methods:
717 patients participating in the Mayo Clinic Bipolar Biobank completed structured diagnostic interviews and questionnaires for demographic and illness-related variables. They also had weight and height measure...
