
Jennifer Urbano BlackfordUniversity of Nebraska Medical Center | UNMC
Jennifer Urbano Blackford
PhD
About
182
Publications
35,697
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
4,782
Citations
Introduction
Additional affiliations
October 2017 - present
July 2014 - September 2017
October 2006 - June 2014
Education
August 1991 - May 1998
Publications
Publications (182)
In people with schizophrenia, anxiety is highly prevalent and related to numerous negative outcomes; unfortunately, anxiety is both underreported and understudied in schizophrenia. The current review highlights the importance and utility of assessing anxiety in schizophrenia by addressing four main questions: (1) What does anxiety look like through...
Background
Anxiety during early alcohol abstinence, likely resulting from neural changes caused by chronic alcohol use, contributes to high relapse rates. Studies in rodents show heightened activation during early abstinence in the bed nucleus of the stria terminalis (BNST)—a neural hub for anxiety—and its extended anxiety‐related corticolimbic net...
Objective: Specific phobia is a common anxiety disorder, but the literature on associated brain structure alterations exhibits substantial gaps. The ENIGMA Anxiety Working Group examined brain structure differences between individuals with specific phobias and healthy control subjects as well as between the animal and blood-injection-injury (BII) s...
Objective:
Specific phobia is a common anxiety disorder, but the literature on associated brain structure alterations exhibits substantial gaps. The ENIGMA Anxiety Working Group examined brain structure differences between individuals with specific phobias and healthy control subjects as well as between the animal and blood-injection-injury (BII)...
Decades of psychosis research highlight the prevalence and the clinical significance of negative emotions, such as fear and anxiety. Translational evidence demonstrates the pivotal role of the amygdala in fear and anxiety. However, most of these approaches have used hypothesis-driven analyses with predefined regions of interest. A data-driven analy...
Objective:
Anxiety disorders are among the most common psychiatric disorders in youths and emerge during childhood. This is also a period of rapid white matter (WM) development, which is critical for efficient neuronal communication. Previous work in preadolescent children with anxiety disorders demonstrated anxiety disorder-related reductions in...
This article presents a unique framework that combines insights from neuroscience with clinical assessment to evaluate individuals who have co-occurring alcohol use disorder, anxiety, and trauma. Through the use of a case study, the authors demonstrate the practical application of this framework and contextualize the relevant neurocircuitry associa...
Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Con...
Neuroanatomical findings on youth anxiety disorders are notoriously difficult to replicate, small in effect size and have limited clinical relevance. These concerns have prompted a paradigm shift toward highly powered (that is, big data) individual-level inferences, which are data driven, transdiagnostic and neurobiologically informed. Here we buil...
Neuroanatomical findings on youth anxiety disorders are notoriously difficult to replicate, small in effect size and have limited clinical relevance. These concerns have prompted a paradigm shift toward highly powered (that is, big data) individual-level inferences, which are data driven, transdiagnostic and neurobiologically informed. Here we buil...
Purpose of Review
Emotions are prominent in theories and accounts of schizophrenia but are largely understudied compared to cognition. Utilizing the Research Domain Criteria (RDoC) Negative Valence Systems framework, we review the current knowledge of emotions in schizophrenia. Given the pivotal role of threat responses in theories of schizophrenia...
Posttraumatic stress disorder (PTSD) is associated with lower cortical thickness (CT) in prefrontal, cingulate, and insular cortices in diverse trauma-affected samples. However, some studies have failed to detect differences between PTSD patients and healthy controls or reported that PTSD is associated with greater CT. Using data-driven dimensional...
Background
Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generaliz...
Posttraumatic stress disorder (PTSD) significantly impacts many veterans. Although PTSD has been linked to alterations in the fear brain network, the disorder likely involves alterations in both the fear and anxiety networks. Fear involves responses to imminent, predictable threat and is driven by the amygdala, whereas anxiety involves responses to...
Aims:
Maintaining abstinence from alcohol use disorder (AUD) is extremely challenging, partially due to increased symptoms of anxiety and stress that trigger relapse. Rodent models of AUD have identified that the bed nucleus of the stria terminalis (BNST) contributes to symptoms of anxiety-like behavior and drug-seeking during abstinence. In human...
There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a gl...
Background: Current clinical assessments of Posttraumatic stress disorder (PTSD) rely solely on subjective symptoms and experiences reported by the patient, rather than objective biomarkers of the illness. Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. Here...
Neuroimaging studies point to neurostructural abnormalities in youth with anxiety disorders. Yet, findings are based on small-scale studies, often with small effect sizes, and have limited generalizability and clinical relevance. These issues have prompted a paradigm shift in the field towards highly powered (i.e., big data) individual-level infere...
Background
The cerebellum critically contributes to higher-order cognitive and emotional functions such fear learning and memory. Prior research on cerebellar volume in PTSD is scant and has neglected neuroanatomical subdivisions of the cerebellum that differentially map on to motor, cognitive, and affective functions.
Methods
We quantified cerebe...
Background
Hippocampal abnormalities are among the most consistent findings in schizophrenia. Numerous studies have reported deficits in hippocampal volume, function, and connectivity in the chronic stage of illness. While hippocampal volume and function deficits are also present in the early stage of illness, there is mixed evidence of both higher...
Excessive fear responses to uncertain threat are a key feature of anxiety disorders (ADs), though most mechanistic work considers adults. As ADs onset in childhood and confer risk for later psychopathology, we sought to identify conditions of uncertain threat that distinguish 8–17-year-old youth with AD (n = 19) from those without AD (n = 33), and...
Temperament involves stable behavioral and emotional tendencies that differ between individuals, which can be first observed in infancy or early childhood and relate to behavior in many contexts and over many years.1 One of the most rigorously characterized temperament classifications relates to the tendency of individuals to avoid the unfamiliar a...
Several studies have examined the acquisition and extinction of fear in PTSD in the context of Pavlovian conditioning. However, research examining reconditioning of fear following extinction, a form of post-extinction re-emergence of conditioned behavior is limited. Although the 5-HT3A receptor gene polymorphism has been linked to trauma responses,...
Neuroimaging studies have revealed hippocampal hyperactivity in schizophrenia. In the early stage of the illness, hyperactivity is present in the anterior hippocampus and is thought to spread to other regions as the illness progresses. However, there is limited evidence for changes in basal hippocampal function following the onset of psychosis. Res...
Background
Shape analyses of patients with schizophrenia have revealed bilateral deformations of the anterolateral hippocampus, primarily localized to the CA1 subfield. Incomplete hippocampal inversion (IHI), an anatomical variant of the human hippocampus resulting from an arrest during neurodevelopment, is more prevalent and severe in patients wit...
The COVID-19 pandemic imposed profound effects on health and daily life, with widespread stress exposure and increases in psychiatric symptoms. Despite these challenges, pandemic research provides unique insights into individual differences in emotion and cognition that predict responses to stress, with general implications for understanding stress...
Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging meth...
Background
Posttraumatic stress disorder (PTSD) is associated with markers of accelerated aging. Estimates of brain age, compared to chronological age, may clarify the effects of PTSD on the brain and may inform treatment approaches targeting the neurobiology of aging in the context of PTSD.
Method
Adult subjects (N = 2229; 56.2% male) aged 18–69...
Substantial evidence from studies in humans suggests the amygdala is pivotal for anxiety. Findings from animal models and translational studies suggests the bed nucleus of the stria terminalis (BNST) is also critical for anxiety and the anticipation of unpredictable threat in adults. However, it remains unknown whether the BNST is involved in unpre...
Importance
Transgender and gender diverse (TGD) individuals, who have a gender identity that differs from their sex assigned at birth, are at increased risk of mental health problems, including depression, anxiety, self-injurious behavior, and suicidality, relative to cisgender peers.
Objective
To examine mental health outcomes among TGD vs cisgen...
The insula is a heterogeneous cortical region, comprised of three cytoarchitecturally distinct sub-regions (agranular, dysgranular, and granular), which traverse the anterior-posterior axis and are differentially involved in affective, cognitive, and somatosensory processing. Smaller insula volume is consistently reported in psychosis-spectrum diso...
In schizophrenia, impairments in affect are prominent and anxiety disorders are prevalent. Neuroimaging studies of fear and anxiety in schizophrenia have focused on the amygdala and show alterations in connectivity. Emerging evidence suggests that the bed nucleus of the stria terminalis (BNST) also plays a critical role in anxiety, especially durin...
Examining volumetric differences of the amygdala and anterior-posterior regions of the hippocampus is important for understanding cognition and clinical disorders. However, the gold standard manual segmentation of these structures is time and labor-intensive. Automated, accurate, and reproducible techniques to segment the hippocampus and amygdala a...
Background
Cross-sectional studies indicate that hippocampal function is abnormal across stages of psychosis. Neural theories of psychosis pathophysiology suggest that dysfunction worsens with illness stage. Here, we test the hypothesis that hippocampal function is impaired in the early stage of psychosis and declines further over the next 2 years....
Background
For individuals with Alcohol Use Disorder (AUD), long‐term recovery is difficult in part due to symptoms of anxiety that occur during early abstinence and can trigger relapse. Research in rodent models of AUD has identified the bed nucleus of the stria terminalis (BNST), a small, sexually dimorphic, subcortical region, as critical for re...
Introduction
The development of neurotransmitter based cognitive enhancers for Alzheimer's disease have focused recently on allosteric modulation, as a way of reducing potential drug-limiting toxicities that have been the hallmark of earlier orthosteric compounds. VU319 is an investigational positive allosteric modulator of the M1 muscarinic acetyl...
Translational models of fear conditioning and extinction have elucidated a core neural network involved in the learning, consolidation, and expression of conditioned fear and its extinction. Anxious or trauma-exposed brains are characterized by dysregulated neural activations within regions of this fear network. In this study, we examined how the f...
Incomplete hippocampal inversion (IHI) is an anatomical variant of the human brain resulting from an arrest in brain development, especially prevalent in the left hemisphere. We hypothesized that IHI is more common in schizophrenia and contributes to the well-known hippocampal structural differences. We studied 199 schizophrenia patients and 161 he...
Neural habituation, the decrease in brain response to repeated stimuli, is a fundamental, highly conserved mechanism that acts as an essential filter for our complex sensory environment. Convergent evidence indicates neural habituation is disrupted in both early and chronic stages of schizophrenia, with deficits co-occurring in brain regions that s...
The bed nucleus of the stria terminalis (BNST) is a medial basal forebrain structure that modulates the hypothalamo-pituitary-adrenal (HPA) axis. The heterogeneous subnuclei of the BNST integrate inputs from mood and reward-related areas and send direct inhibitory projections to the hypothalamus. The connections between the BNST and hypothalamus ar...
Relational memory is impaired in psychotic disorders. In non-affective psychotic disorders, relational memory deficits are present in the early stage of illness and become more pronounced in the chronic stage. Previous studies have demonstrated cognitive deficits in early-stage psychotic bipolar disorder, but it is unclear whether relational memory...
Background
The investigational new drug VU319 has recently completed first‐in‐human testing in a Phase 1 Single Ascending Dose (SAD) study, which included a Food Effect substudy. The main objectives of the SAD study were to assess the safety and tolerability of VU319 in healthy adults. The Food Effect substudy examined whether the metabolism and ab...
Background
VU319 is an investigational positive allosteric modulator of the M 1 muscarinic acetylcholine receptor developed for cognitive enhancement in Alzheimer’s disease (AD) and other disorders. Cognitive tasks including test of attention, speed, and memory and event‐related potentials (ERPs) were used during the double‐blind, placebo controlle...
Objective:
Thalamus models of psychosis implicate association nuclei in the pathogenesis of psychosis and mechanisms of cognitive impairment. Studies to date have provided conflicting findings for structural deficits specific to these nuclei. The authors sought to characterize thalamic structural abnormalities in psychosis and a neurodevelopmental...
Cross-sectional studies suggest that hippocampal volume declines across stages of psychosis. In contrast, longitudinal studies indicate that hippocampal volume is stable in the critical period following illness onset. How can these seemingly disparate sets of findings be resolved? In the present study, we examine two previously unexplored reasons f...
Background:
Relational memory, the ability to bind information into complex memories, is moderately impaired in early psychosis and severely impaired in chronic schizophrenia, suggesting relational memory may worsen throughout the course of illness.
Methods:
We examined relational memory in 66 early psychosis patients and 64 healthy control subj...
Background
Memory is significantly impaired in schizophrenia. However, memory measures are often complex and confounded by additional impairments such as motivation and task comprehension, which can affect behavioral performance and obscure neural function during memory tasks. Neural signatures of memory encoding that are robust to potential confou...
Anxiety disorders are the most prevalent mental health conditions among US youth, with more than 30% experiencing an anxiety disorder by the time they reach age 18 years.¹ Childhood anxiety is associated with significant impairment across family, social, and academic domains, typically affecting every area of life. Longitudinal research suggests th...
Background
The conceptualization of risk for psychiatric illness is moving from risk factors for specific psychiatric disorders to factors that confer risk for multiple disorders. One potential transdiagnostic risk factor is inhibited temperament, a trait characterized by a fearful or avoidant response to novelty. Inhibited temperament is an establ...
Introduction
The development of neurotransmitter based cognitive enhancers for Alzheimer's disease have focused recently on allosteric modulation, as a way of reducing potential drug-limiting toxicities that have been the hallmark of earlier orthosteric compounds. VU319 is an investigational positive allosteric modulator of the M1 muscarinic acetyl...
The insula is structurally abnormal in schizophrenia, demonstrating reductions in volume, cortical thickness, and altered gyrification during prodromal, early and chronic stages of the illness. Despite compelling structural alterations, less is known about its functional connectivity, limited by studies considering the insula as a whole or only wit...
Background:
Anatomical connectivity between the thalamus and cortex, including the prefrontal cortex (PFC), is abnormal in schizophrenia. Overlapping phenotypes, including deficits in executive cognitive abilities dependent on PFC-thalamic circuitry, suggest dysrupted thalamocortical anatomical connectivity may extend to psychotic bipolar disorder...
Alcohol Use Disorder (AUD) is a chronic, relapsing disease that impacts almost a third of Americans. Despite effective treatments for attaining sobriety, the majority of patients relapse within a year, making relapse a substantial barrier to long‐term treatment success. A major factor contributing to relapse is heightened negative affect that resul...
The bed nucleus of the stria terminalis (BNST) is emerging as a critical region in multiple psychiatric disorders including anxiety, PTSD, and alcohol and substance use disorders. In conjunction with growing knowledge of the BNST, an increasing number of studies examine connections of the BNST and how those connections impact BNST function. The imp...
The insula is structurally abnormal in schizophrenia, demonstrating robust reductions in gray matter volume, cortical thickness, and altered gyrification during prodromal, early and chronic stages of the illness. Despite compelling structural alterations, less is known about its functional connectivity, limited by studies considering the insula as...
Objective:
In schizophrenia, the anterior hippocampus is hyperactive and shows reduced task-related recruitment, but the relationship between these two findings is unclear. The authors tested the hypothesis that hyperactivity impairs recruitment of the anterior hippocampus during scene processing.
Methods:
Functional MRI data from 45 early-psych...
Background: Social anxiety disorder (SAD) is an incapacitating disorder running in
families. Previous work associated social fearfulness with a failure to habituate, but the
habituation response to neutral faces has, as of yet, not been investigated in patients with
SAD and their family members concurrently. Here, we examined whether impaired
habit...
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Background:
Across networks, connectivity within the frontoparietal network (FPN) and cingulo-opercular network (CON) exhibits reductions earliest during healthy aging, contributing to cognitive impairment. Individuals with psychotic disorders demonstrate evidence of accelerated aging across multiple biological systems. By leveraging a large sampl...
Background:
Humans constantly take in vast amounts of information, which must be filtered, flexibly manipulated, and integrated into cohesive relational memories in order to choose relevant behaviors. Relational memory is impaired in chronic schizophrenia, which has been linked to hippocampal dysfunction. It is unclear whether relational memory is...
Working memory (WM) is impaired in psychotic disorders and linked to functional outcome. Most neurobiological models emphasize prefrontal cortex (PFC) dysfunction in the etiology of WM impairment. However, WM is composed of multiple processes, including encoding and maintenance, and the delineation of the neurobiology of these sub-processes has not...
Background:
Learning and memory are impaired in schizophrenia. Some theories have proposed that one form of memory, habituation, is particularly impaired. Preliminary evidence suggests that memory impairment is associated with failed hippocampal habituation in patients with chronic schizophrenia. We studied how abnormal habituation of the hippocam...
Background
Neuropsychological impairment is common in schizophrenia and psychotic bipolar disorder. It has been hypothesized that the pathways leading to impairment differ between disorders. Specifically, cognitive impairment in schizophrenia is believed to result largely from atypical premorbid neurodevelopment, whereas bipolar disorder is increas...
Background
Across functional networks, connectivity within the fronto-parietal (FPN) and cingulo-opercular (CON) networks declines earliest during healthy aging, contributing to cognitive impairment. Individuals with psychotic disorders demonstrate evidence of accelerated aging across multiple biological systems, including brain structure and funct...
Background
Diagnostic categories are a fundamental piece of psychiatric disorders; however, a patient’s symptoms and behaviors seldom fit under one diagnosis. Transdiagnostic approaches have been proposed with a goal of identifying mechanisms that share commonalities across diagnoses, instead of identifying differences. Transdiagnostic vulnerabilit...