Susan L Mcelroy

University of Cincinnati | UC · Department of Psychiatry

Background Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the in...

Background Epidemiological data offer conflicting views of the natural course of binge-eating disorder (BED), with large retrospective studies suggesting a protracted course and small prospective studies suggesting a briefer duration. We thus examined changes in BED diagnostic status in a prospective, community-based study that was larger and more...

The link between bipolar disorder (BP) and immune dysfunction remains controversial. While epidemiological studies have long suggested an association, recent research has found only limited evidence of such a relationship. To clarify this, we performed an exploratory study of the contributions of immune-relevant genetic factors to the response to l...

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...

Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extra...

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...

Bipolar disorder (BD) is a heritable mental illness with complex etiology. While the largest published genome-wide association study identified 64 BD risk loci, the causal SNPs and genes within these loci remain unknown. We applied a suite of statistical and functional fine-mapping methods to these loci, and prioritized 22 likely causal SNPs for BD...

Background Obesity is common among persons with bipolar disorder (BD). Liraglutide 3.0 mg/d subcutaneous injection is indicated for chronic weight management and associated with minimal adverse neuropsychiatric effects. This study evaluated whether liraglutide 3 mg/d reduced body weight, improved metabolic factors and eating psychopathology, and wa...

Glucagon‐like peptide‐1 receptor agonists (GLP‐1As) are being used as approved or off‐label treatments for weight loss. As such, there has been increasing concern about the potential for GLP‐1As to impact eating disorder (ED) symptomatology. This article seeks to (1) review the current state of knowledge regarding GLP‐1As and ED symptomatology; (2)...

Converging theoretical frameworks suggest a role and a therapeutic potential for spinal interoceptive pathways in major depressive disorder (MDD). Here, we aimed to evaluate the antidepressant effects and tolerability of transcutaneous spinal direct current stimulation (tsDCS) in MDD. This was a double-blind, randomized, sham-controlled, parallel g...

Background: Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the i...

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....

Objective: This Phase II, placebo-controlled, double-blind study investigated the efficacy, safety, and tolerability of nivasorexant in the treatment of adults with moderate to severe binge-eating disorder (BED). Methods: Adults meeting the DSM-5 BED criteria were randomized 1:1 to placebo or nivasorexant (100 mg b.i.d.). The primary endpoint wa...

Objectives: This study examined the use of a self-monitoring/self-management smartphone application (app) for patients with bipolar disorder. The app was specifically designed with patient-centered computational software system based on concepts from nonlinear systems (chaos) theory. Methods: This was a randomized, active comparator study of use...

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 There is emerging evidence that stimulants warrant further investigation as a treatment for bulimia nervosa (BN) including a recent open-label feasibility trial examining the use of lisdexamfetamine dimestylate (LDX) for BN. The current report presents the secondary outcomes and qualitative interview results from that feasibility trial....

Background Converging theoretical frameworks suggest a role and a therapeutic potential for spinal interoceptive pathways in major depressive disorder (MDD). We aimed to evaluate the antidepressant effects and tolerability of transcutaneous spinal direct current stimulation (tsDCS) in MDD. Methods This was a double-blind, randomized, sham-controll...

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...

Background Major Depressive Disorder (MDD) and obesity are bidirectionally related, but the amount of weight-gain secondary to MDD is unknown. We aimed to estimate the adjusted effect of MDD on weight-change in prospective studies compared to individuals without MDD. Methods Scopus/MEDLINE, PsycInfo, Web of Science and Cochrane were systematically...

Lithium has been a cornerstone treatment for bipolar disorder (BD). Despite descriptions in the literature regarding associations between long-term lithium therapy (LTLT) and development of a thyroid disorder (overt/subclinical hypo/hyperthyroidism, thyroid nodule, and goiter) in BD, factors such as time to onset of thyroid abnormalities and impact...

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...

Purpose: Long-term lithium therapy (LTLT) has been associated with chronic kidney disease (CKD). We investigated changes in clinical characteristics, pharmacotherapeutic treatments for medical/psychiatric disorders, and outcomes among patients with bipolar disorder (BD) and CKD on LTLT in a 2-year mirror-image study design. Methods: Adult BD pati...

Randomized, placebo‐controlled trials for binge eating disorder (BED) have revealed highly variable, and often marked, rates of short‐term placebo response. Several quantitative based analyses in patients with BED have inconsistently demonstrated which patient factors attribute to an increase in placebo response. The objective of this study is to u...

Purpose: Although clozapine was Food and Drug Administration (FDA) approved more than 3 decades ago by the FDA, major barriers and gaps in knowledge continue to prevent its effective and safe use. We review modern-day problems encountered with clozapine in the United States (US). Methods: Information surrounding current administrative, clinical, r...

Background Emerging research suggests that food intake timing, eating behavior and food preference are associated with aspects of the circadian system function but the role that the circadian system may play in binge eating (BE) behavior in humans remains unclear. Objective To systematically evaluate the evidence for circadian system involvement i...

Objective Few instruments measuring life events over the course of bipolar disorder distinguish the valence of events or consider cumulative stress burden. In the current study, we used a valence-focused life event questionnaire to assess stress in the last 12 months in patients with bipolar I (n = 863) and bipolar II (n = 362) disorder. Methods A...

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...

Objective Bipolar patients in the United States (US) compared to those from the Netherlands and Germany (here abbrev. as “Europe”) have more Axis I comorbidities and more poor prognosis factors such as early onset and psychosocial adversity in childhood. We wished to examine whether these differences also extended to Axis II personality disorders (...

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...

Objectives: Persistent functional impairment is common in bipolar disorder (BD) and is influenced by a number of demographic, clinical, and cognitive features. The goal of this project was to estimate and compare the influence of key factors on community function in multiple cohorts of well-characterized samples of individuals with BD. Methods:...

Background Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment. Aims To use a combination of transdiagnostic genetic and clinical factors to predict l...

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 Patients with bipolar disorder treated with lithium often require additional antipsychotics or anticonvulsants. However, the comparative effectiveness and safety of these agents as add-on to lithium has not been studied. Methods This secondary analysis combined two similar 24-week trials on outpatients with bipolar disorder randomized to...

AimThis study quantified and compared demographic and clinical features of bipolar disorder (BD) in persons of African ancestry (AA) and European ancestry (EUR).Methods Participants enrolled in the Mayo Clinic Bipolar Biobank from 2009 to 2015. The structured clinical interview for DSM-IV was used to confirm the diagnosis of BD, and a questionnaire...

Hirschsprung disease (HD) is a congenital disease which occurs in about 1 in 5000 births and is most commonly diagnosed shortly after birth. True incidence of HD in adulthood is unknown, because the illness is often undiagnosed or misdiagnosed in the adult population. A variety of nonspecific gastrointestinal complains (constipation, abdominal disc...

Background Patients with bipolar disorder have higher rates of cardiometabolic comorbidities and mortality. Although guidelines emphasize the importance of cardiovascular monitoring, few studies characterized the cardiometabolic risk profile during treatment and their relation to symptomatology and treatment response. Methods We analyzed data from...

Background Many individuals with eating disorders remain symptomatic after a course of psychotherapy and pharmacotherapy; therefore, the development of innovative treatments is essential. Method To learn more about the current evidence for treating eating disorders with stimulants, we searched for original articles and reviews published up to Apri...

Lithium is the gold standard therapy for Bipolar Disorder (BD) but its effectiveness differs widely between individuals. The molecular mechanisms underlying treatment response heterogeneity are not well understood, and personalized treatment in BD remains elusive. Genetic analyses of the lithium treatment response phenotype may generate novel molec...

Response to lithium varies widely between individuals with bipolar disorder (BD). Polygenic risk scores (PRSs) can uncover pharmacogenomics effects and may help predict drug response. Patients ( N = 2,510) with BD were assessed for long-term lithium response in the Consortium on Lithium Genetics using the Retrospective Criteria of Long-Term Treatme...

Background Depending on the classification system used, 5–40% of manic subjects present with concomitant depressive symptoms. This post-hoc analysis evaluates the hypothesis that (hypo)manic subjects have a higher burden of depression than non-(hypo)manic subjects. Methods Data from 806 Bipolar I or II participants of the Stanley Foundation Bipola...

Introduction Binge eating disorder (BED) is an important public health problem associated with severe psychosocial and medical consequences for which treatment options are limited. The objective of this study is to evaluate the efficacy and tolerability of the novel dopamine and norepinephrine reuptake inhibitor (DNRI) solriamfetol in the treatment...

Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLi...

Background Suicide is a leading cause of death worldwide, and non-fatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genom...

Background Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools. Aims To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristi...

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...

Background We aimed to study the probability of bipolar depression response at 24 weeks given initial non-response. Methods We combined two multi-site, 24-week trials including similar populations following the same evidence-based guidelines randomizing patients to lithium or quetiapine. Additional mood-stabilizing treatment was possible if clinic...

Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in pat...

Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, par...

Bipolar disorder often follows a set progression best described in stages where advanced stages are associated with poorer outcomes. Bipolar disorder is also often characterized by a predominance of episode polarity, where some individuals experience more depressive episodes (termed predominant depressive polarity) while others experience more hypo...

Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, par...

Background: Studying the phenotypic and genetic characteristics of age and polarity at onset (AAO, PAO) in bipolar disorder (BD) can provide new insights into disease pathology and facilitate the development of screening tools. Aims: To examine the genetic architecture of AAO and PAO and their association with BD disease characteristics. Methods: G...

Background The Stanley Foundation Bipolar Treatment Outcome Network (SFBN) recruited more than 900 outpatients from 1995 to 2002 from 4 sites in the United States (US) and 3 in the Netherlands and Germany (abbreviated as Europe). When funding was discontinued, the international group of investigators continued to work together as the Bipolar Collab...

Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred...

Introduction A key mechanism of lithium is the inhibition of glycogen synthase kinase‐3β (GSK3β) and activation of mammalian target of rapamycin (mTOR), two contributors to insulin signaling. We explored the relationship between these markers and clinical response to lithium in bipolar disorder (BD). Methods Thirty‐four subjects with BD who had be...

Introduction Approximately 70% of patients with bipolar disorder (BPD) are initially misdiagnosed, resulting in significantly delayed diagnosis of 7–10 years on average. Misdiagnosis and diagnostic delay adversely affect health outcomes and lead to the use of inappropriate treatments. As depressive episodes and symptoms are the predominant symptom...

Objective: Self-management of bipolar disorder (BD) is an important component of treatment. Methods: We developed a patient-centered computational software system based on concepts from nonlinear systems (chaos) theory with mobile access to assist in managing BD known as KIOS. KIOS tracks interacting symptoms to determine theprecise state of a B...

Growing evidence indicates that historical descriptions of mixed depression—broadly defined as major depressive episodes with subthreshold manic or hypomanic (hypo/manic) symptoms—are incredibly clinically relevant in this day-and-age. However, the first operational definition of mixed depression did not occur in the modern nomenclature until 2013...

Background Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods We conducted the largest to...

Aims: Long-term lithium-therapy (LTLT) has been associated with kidney insufficiency in bipolar disorder (BD). We aimed to investigate the risk factors of chronic kidney disease (CKD) development and progression among BD patients receiving LTLT. Methods: We included adult patients with BD on LTLT (≥1year) who were enrolled in the Mayo Clinic Bip...

Objective: This study examined the feasibility, safety, and potential efficacy of lisdexamfetamine (LDX) as a treatment for adults with bulimia nervosa (BN). Method: An open-label 8-week feasibility study was conducted in participants with BN. Enrollment rate, dropout rate, safety outcomes, and eating disorder symptom change were examined. Resu...

BACKGROUND: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. / METHODS: We conducted the largest...

Antipsychotic drugs are efficacious first-line treatments for many individuals diagnosed with a psychiatric illness. However, their adverse metabolic side-effect profile, which resembles the metabolic syndrome, represents a significant clinical problem that increases morbidity and limits treatment adherence. Moreover, the mechanisms involved in ant...

Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLi...

Objective Depressive episodes and symptoms of bipolar I disorder are commonly misdiagnosed as major depressive disorder (MDD) in primary care. The novel and pragmatic Rapid Mood Screener (RMS) was developed to screen for manic symptoms and bipolar I disorder features (e.g., age of depression onset) to address this unmet clinical need. Methods A ta...

Suicide is a leading cause of death worldwide and non-fatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both are known to have a substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. We conducted a genome-wide...

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...

Bipolar disorder (BD) has high clinical heterogeneity, frequent psychiatric comorbidities, and elevated suicide risk. To determine genetic differences between common clinical sub-phenotypes of BD, we performed a systematic polygenic risk score (PRS) analysis using multiple PRSs from a range of psychiatric, personality, and lifestyle traits to disse...

Bipolar disorder (BD) is a heritable mental illness with complex etiology. We performed a genome-wide association study (GWAS) of 41,917 BD cases and 371,549 controls, which identified 64 associated genomic loci. BD risk alleles were enriched in genes in synaptic and calcium signaling pathways and brain-expressed genes, particularly those with high...

Objective: Binge-eating disorder (BED) is the most prevalent eating disorder; however, few evidence-based treatments are available. The aim of this study was to evaluate the efficacy and safety of dasotraline, a novel dopamine and norepinephrine reuptake inhibitor, in adults with BED. Methods: Patients with a DSM-5 diagnosis of BED (intent-to-tr...

BACKGROUND Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. METHODS We conducted the largest to...

Several anti‐epileptic drugs (AED) have FDA approval for use as mood stabilizers in bipolar disorder (BD), but not all BD patients respond to these AED mood stabilizers (AED‐MS). To identify genetic polymorphisms that contribute to the variability in AED‐MS response, we performed a discovery genome‐wide association study of 199 BD patients from the...

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...

Background Evidence is emerging that early onset bipolar disorder and the duration of the delay to first treatment are both risk factors for poor treatment outcome. We report on the incidence and implications of these two risk factors in patients from the United States (US) versus Europe. Methods Age of onset and age at first treatment for depress...

Introduction: There is a high incidence of Axis II personality disorders (PDs) in patients with bipolar illness, but their influence on the prospectively measured course of bipolar disorder has been less well explicated. Methods; 392 outpatients with bipolar disorder gave informed consent, completed the PDQ4 99 item personality disorder rating, and...

Background Adjunctive antidepressants are frequently used for bipolar depression but their clinical efficacy has been studied in few trials and little is known about how co‐occurring manic symptoms affect treatment response. Methods Bipolar Clinical Health Outcomes Initiative in Comparative Effectiveness (N = 482) and Lithium Treatment Moderate‐Do...

This chapter reviews the use of medications in the treatment of individuals with bulimia nervosa (BN) and binge-eating disorder (BED), the two mental disorders defined by the presence of binge eating. Drug classes evaluated include antidepressants, stimulants, and other medications for attention-deficit/hyperactivity disorder (ADHD), antiepileptic...

Objective.: The aim of this fixed-dose study was to evaluate the efficacy and safety of dasotraline in the treatment of patients with binge-eating disorder (BED). Methods.: Patients meeting Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for BED were randomized to 12 weeks of double-blind treatment with fixed doses...

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...

Bipolar disorder (BD) has high clinical heterogeneity, frequent psychiatric comorbidities, and elevated suicide risk. To determine genetic differences between common clinical sub-phenotypes of BD, we performed a systematic PRS analysis using multiple polygenic risk scores (PRSs) from a range of psychiatric, personality, and lifestyle traits to diss...