Elizabeth D Ballard

National Institute of Mental Health, National Institutes of Health | NIMH · Experimental Therapeutics and Pathophysiology

The COVID-19 pandemic’s impact on mental health is challenging to quantify because pre-existing risk, disease burden and public policy varied across individuals, time and regions. Longitudinal, within-person analyses can determine whether pandemic-related changes in social isolation impacted mental health. We analyzed time-varying associations betw...

Previous studies have suggested that alterations in white matter (WM) microstructure are implicated in suicidal thoughts and behaviours (STBs). However, findings of diffusion tensor imaging (DTI) studies have been inconsistent. In this large-scale mega-analysis conducted by the ENIGMA Suicidal Thoughts and Behaviours (ENIGMA-STB) consortium, we exa...

Psychiatric genetic counseling (GC) has been associated with patient-reported increases in empowerment (perceived control, emotional regulation, and hope). We sought to evaluate the extent to which patients' psychological state at the time of GC is related to changes in empowerment. Participants with a history of major depressive disorder and/or bi...

Aggression and impulsivity are linked to suicidal behaviors, but their relationship to the suicidal crisis remains unclear. This magnetoencephalography (MEG) study investigated the link between aggression, impulsivity, and resting-state MEG power and connectivity. Four risk groups were enrolled: high-risk (HR; n=14), who had a recent suicidal crisi...

The glutamatergic modulator ketamine is associated with changes in sleep, depression, and suicidal ideation (SI). This study sought to evaluate differences in arousal-related sleep metrics between 36 individuals with treatment-resistant major depression (TRD) and 25 healthy volunteers (HVs). It also sought to determine whether ketamine normalizes a...

The impact of the COVID-19 pandemic on mental health is challenging to quantify because factors such as pre-existing risk, disease burden, and public policy varied across individuals, time, and regions. To understand dynamic relationships between these factors, we analyzed time-varying associations between psychiatric vulnerability, loneliness, psy...

Trauma and stressor-related symptoms have been frequently reported during the COVID-19 pandemic. Few studies compare post-traumatic stress symptoms (PTSS) between patients and non-infected controls. Using data from an ongoing natural history study of COVID-19, this study compared PTSS between patients infected with SARS-CoV-2 during the first year...

Background An urgent need exists to identify neural correlates associated with differing levels of suicide risk and develop novel, rapid-acting therapeutics to modulate activity within these neural networks. Methods Electrophysiological correlates of suicide were evaluated using magnetoencephalography (MEG) in 75 adults with differing levels of su...

Introduction: Safety planning type interventions (SPTI's) are brief suicide-specific interventions. Little is known about safety plan use during high-risk periods, and whether safety plan use is influenced by baseline characteristics. This study examined how adolescents recently hospitalized for suicide risk use their safety plans post-discharge,...

Although suicide is a leading cause of preventable death worldwide, current prevention efforts have failed to substantively mitigate suicide risk. Suicide research has traditionally relied on subjective reports that may not accurately differentiate those at high versus minimal risk. This narrative review supports the inclusion of objective task-bas...

Biomarkers that can differentiate between psychiatric disorders with and without suicidal behavior history from each other and from healthy volunteers may explain part of the pathogen-esis of suicidal behavior. We conducted the hitherto largest meta-analysis comparing immune biomarkers between subjects with and without suicide attempt history or de...

The novel mechanisms of action (MOA) derived from some recently introduced molecular targets have led to regulatory approvals for rapid acting antidepressants (RAADs) that can generate responses within hours or days, rather than weeks or months. These novel targets include the N-methyl-D-glutamate receptor antagonist ketamine, along with its enanti...

Objective: A major limitation of current suicide research is the lack of power to identify robust correlates of suicidal thoughts or behavior. Variation in suicide risk assessment instruments used across cohorts may represent a limitation to pooling data in international consortia. Method: Here, we examine this issue through two approaches: (a) an...

Suicide is a leading cause of death among young people every year. Identifying risk factors provides opportunities to intervene, and social anxiety may represent one such factor. This systematic review and meta-analysis aimed to review the evidence of associations between social anxiety and suicidality in youth (10–25 years). Embase, PsycInfo, and...

Depression is disabling and highly prevalent. Intravenous (IV) ketamine displays rapid-onset antidepressant properties, but little is known regarding which patients are most likely to benefit, limiting personalized prescriptions. We identified randomized controlled trials of IV ketamine that recruited individuals with a relevant psychiatric diagnos...

Background Clinical trials of intravenous (IV) racemic (R,S)-ketamine (hereafter referred to as IV ketamine) have consistently reported rapid and substantial reductions in overall depressive symptoms compared with saline (inactive placebo) or midazolam (active placebo). However, the evidence for IV ketamine’s specific effects on suicidal ideation i...

Background This study sought to examine the association between prospective suicidal behavior and variability, intensity, and persistence of suicidal ideation (SI) in bipolar disorder (BD). Methods Data were drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), a naturalistic study of 4360 outpatients 15 years or...

Background: This study examined magnetoencephalographic (MEG) correlates of suicidal ideation (SI) and suicide attempt history in patients with treatment-resistant major depression (TRD) at baseline and following subanesthetic-dose ketamine infusion. Methods: Twenty-nine drug-free TRD patients (12 suicide attempters/17 non-attempters) participat...

Suicide is a leading cause of death in young adulthood. Identifying early prevention targets to reduce later suicide is a public health priority. Impulsivity and aggression in early childhood may represent actionable early prevention candidate endophenotypes for later suicidal behavior. Our objective is to to understand the association of aggressio...

Background Early markers preceding suicide ideation (SI) may provide valuable information for both assessment and treatment. The glutamatergic modulator ketamine has rapid, transient effects on SI, creating an opportunity to observe potential antecedents of the re-emergence of SI. This analysis evaluated whether the interaction between two suicide...

Suicide is a leading cause of death and morbidity worldwide, yet few interventions are available to mitigate its risk. Barriers to effective treatments involve a limited understanding of factors that predict the onset of suicidal thoughts and behaviors. In the context of suicide risk, stress is a precipitating factor that is largely overlooked in t...

A better understanding of suicidal ideation (SI), including patterns of SI, may help elucidate links between depression, SI, and suicidal behavior. This study sought to identify trajectories of SI in a large, community-based clinical trial of participants with major depressive disorder (MDD) and to investigate the relationships between these trajec...

Pharmacologic and non-pharmacologic treatment of children and adolescents with suicidal thoughts and behavior have lagged behind the already sparse treatments for suicidal adults, leaving many at-risk youths undertreated. The following is a review of the neurobiological research literature focused on suicide risk in children and adolescents. Topics...

Background Suicide is a global health crisis. However, no objective biomarkers of suicide risk currently exist, and self-report data can be unreliable, which limits prediction, diagnostic, and treatment efforts. Reliable biomarkers that can differentiate between diagnostic subgroups, predict worsening symptoms, or suggest novel therapeutic targets...

This study assessed the relationship between contact with COVID-19 patients and the mental health of healthcare workers (HCWs) in the United States (US). In a convenience sample of 957 HCWs who completed an anonymous online survey between April-May 2020, HCWs who provided direct care to confirmed or suspected COVID-19 patients reported increased de...

Background: The COVID 19 pandemic led to dramatic threats to health and social life. Study objectives are to develop a prediction model leveraging subsample of known Patient/Controls and evaluate the relationship of predicted mental health status to clinical outcome measures and pandemic-related psychological and behavioral responses during lockdow...

Objective A major limitation of current suicide research is the lack of power to identify robust correlates of suicidal thoughts or behaviour. Variation in suicide risk assessment instruments used across cohorts may represent a limitation to pooling data in international consortia. Method Here, we examine this issue through two approaches: (i) an e...

Dysfunction in a wide array of systems—including the immune, monoaminergic, and glutamatergic systems—is implicated in the pathophysiology of depression. One potential intersection point for these three systems is the kynurenine (KYN) pathway. This study explored the impact of the prototypic glutamatergic modulator ketamine on the endogenous KYN pa...

Deaths due to suicide are one of the leading causes of mortality among youths and young adults. Active suicidal ideation (SI) is considered one of the strongest risk factors for suicide. Here, we evaluated the neurocircuitry of SI in a sample of youths and young adults (aged 10–26 years) with current or past diagnosis of either major depression or...

Background Nocturnal wakefulness has emerged as a potential predictor of short-term suicide risk. This analysis used dynamic temporal patterns in alpha and beta power and global sleep metrics to explore the possible link between next-day suicidal ideation (NDSI) and wakefulness measures in unmedicated participants with treatment-resistant depressio...

Rapid‐acting treatments for suicidal thoughts are critically needed. Consequently, there is a burgeoning literature exploring psychotherapeutic, pharmacologic, or device‐based brief interventions for suicidal thoughts characterized by a rapid onset of action. Not only do these innovative treatments have potentially important clinical benefits to pa...

Rapid-acting interventions for the suicide crisis have the potential to transform treatment. In addition, recent innovations in suicide research methods may similarly expand our understanding of the psychological and neurobiological correlates of suicidal thoughts and behaviors. This review discusses the limitations and challenges associated with c...

Ketamine produces immediate antidepressant effects and has inspired research into next-generation treatments. Ketamine also has short term dissociative effects, in which individuals report altered consciousness and perceptions of themselves and their environment. However, whether ketamine’s dissociative side effects are necessary for its antidepres...

Limited knowledge exists regarding the neurobiology of suicidal thoughts, given that there are currently no direct probes of the suicidal state. This pilot study used magnetoencephalography (MEG) to evaluate correlates of the implicit association between the self and death compared to the self and life as objective markers of suicide risk. Healthy...

Objective: The objective of this study was to assess whether patient-reported anxiety symptoms are associated with suicide risk in pediatric emergency department (ED) patients. An additional objective was to examine differences between patients presenting for medical/surgical or psychiatric complaints. Methods: Pediatric patients aged 10 to 21 y...

Major depressive disorder (MDD) is highly heterogenous in its clinical presentation. The present exploratory study used magnetoencephalography (MEG) to investigate electrophysiological intrinsic connectivity differences between healthy volunteers and unmedicated participants with treatment-resistant MDD. The study examined canonical frequency bands...

Objective Ketamine’s effects on different dimensions of depressive symptomatology, including typical/melancholic and atypical depression, remain largely unknown. This study examined the effects of a single intravenous dose of ketamine on general depressive symptoms (measured using the Montgomery‐Asberg Depression Rating Scale (MADRS), typical/melan...

Objective Mood disorders, child maltreatment, and medical morbidity are associated with enormous public health burden and individual suffering. The effect of mood disorders on medical morbidity, accounting for child maltreatment, has not been studied prospectively in a large, representative sample of community-dwelling US adults. This study tested...

As a field, psychiatry is undergoing an exciting paradigm shift toward early identification and intervention that will likely minimize both the burden associated with severe mental illnesses as well as their duration. In this context, the rapid-acting antidepressant ketamine has revolutionized our understanding of antidepressant response and greatl...

Major depressive disorder (MDD) is highly prevalent and frequently disabling. Only about 30% of patients respond to a first-line antidepressant treatment, and around 30% of patients are classified as “treatment-resistant” after failing to respond to multiple adequate trials. While most antidepressants target monoaminergic targets, ketamine is an N-...

The image of the Figure 2b in Figure 2 in the published article was incorrect and the authors would like to correct them. The original article has been corrected.

Anhedonia—broadly defined as loss of interest and/or an inability to experience pleasure—is an important feature of several psychiatric disorders. Research into the clinical presentation and neurobiology of this symptom has identified components related to motivation, learning, anticipation, and experience of pleasure as important constructs that i...

Background: Defining the neurobiological underpinnings of suicidal ideation (SI) is crucial to improving our understanding of suicide. This study used magnetoencephalographic gamma power as a surrogate marker for population-level excitation-inhibition balance to explore the underlying neurobiology of SI and depression. In addition, effects of phar...

Objectives: The suicide crisis is a relatively short-lived psychiatric emergency, with transient symptoms that ebb and flow around the suicide attempt.Understanding the dynamic processes of symptoms before and after suicide attempt may aid future prevention efforts. Methods: Data were drawn from the NIMH STEP-BD study, which followed 4,360patien...

Background: Despite decades of research, the rate of death from suicide is rising in the United States. Suicide is a complex and multifactorial phenomenon and, to date, no validated biomarkers that predict suicidal behavior have been identified. Only one FDA-approved drug to prevent suicide exists, and it is approved only for patients with schizop...

Objective: Suicide is a public health threat. Nevertheless, the research literature on actively suicidal participants is relatively sparse, in part because they are often excluded from medical, psychiatric, and psychological research for a host of logistical, ethical, and safety concerns. These obstacles to research participation and enrollment ma...

Ketamine’s mechanism of action was assessed using gamma power from magnetoencephalography (MEG) as a proxy measure for homeostatic balance in 35 unmedicated subjects with major depressive disorder (MDD) and 25 healthy controls enrolled in a double-blind, placebo-controlled, randomized cross-over trial of 0.5 mg/kg ketamine. MDD subjects showed sign...

Background: Visits to the emergency department (ED) for psychiatric purposes are an indicator of chronic and acute unmet mental health needs. In the current study, we examined if psychiatric ED visits among individuals 6 to 24 years of age are increasing nationwide. Methods: ED data came from the 2011-2015 National Hospital Ambulatory Medical Ca...

Objective A critical need exists to identify objective markers of suicide ideation. One potential suicide risk marker is the Suicide Implicit Association Task (S‐IAT), a behavioral task that uses differential reaction times to compare the implicit association between the self and death to the implicit association between the self and life. Individu...

The goal of this study was to infer the effectiveness of midazolam as a comparator in preserving the blind in ketamine studies for mood disorders through patient-level analyses of efficacy trial outcomes. In this integrative data analysis (k = 9, N = 367 patients with mood disorders), clinical outcomes were compared across four groups: ketamine (mi...

Purpose This study examined the links between 24-hour activity patterns (specifically, amplitude and timing of wrist activity) and the persisting qualities of clinical antidepressant response to the glutamatergic modulator ketamine. Methods Twenty-four-hour activity patterns were compared across 5 days of 24-hour activity rhythms in patients with...

Background: Fatigue and depression are closely associated. The purpose of this secondary analysis was to understand the relationships between depression and improvements in specific depression domains on the anti-fatigue effects of ketamine, which we previously reported. Methods: This secondary analysis re-evaluated data collected longitudinally...

Background: Inflammation is associated with major depressive disorder (MDD). Translocator protein 18 kDa (TSPO), a putative biomarker of neuroinflammation, is quantified using positron emission tomography (PET) and 11C-PBR28, a TSPO tracer. We sought to (1) investigate TSPO binding in MDD subjects currently experiencing a major depressive episode,...

Background: No pharmacological treatments exist for active suicidal ideation (SI), but the glutamatergic modulator ketamine elicits rapid changes in SI. We developed data-driven subgroups of SI trajectories after ketamine administration, then evaluated clinical, demographic, and neurobiological factors that might predict SI response to ketamine....