K. Luan Phan

K. Luan Phan
The Ohio State University | OSU · Department of Psychiatry and Behavioral Health

M.D.

About

409
Publications
73,433
Reads
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24,402
Citations
Citations since 2017
184 Research Items
11138 Citations
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Additional affiliations
July 2019 - March 2020
The Ohio State University
Position
  • Chair
February 2012 - June 2019
University of Illinois at Chicago
Position
  • Managing Director
February 2012 - June 2019
Jesse Brown VA Medical Center
Position
  • Chief, Neuropsychiatric Research

Publications

Publications (409)
Article
Full-text available
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...
Article
Full-text available
Rumination and worry are forms of repetitive negative thinking (RNT) commonly associated with internalizing psychopathologies, although less is known about RNT in trauma-exposed individuals with internalizing psychopathologies. Separate lines of research show RNT also plays a role in problematic sleep, which is frequently experienced after trauma e...
Preprint
Full-text available
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...
Preprint
Full-text available
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...
Preprint
Full-text available
A number of studies of posttraumatic stress disorder (PTSD) report thinner cerebral cortical gyri using gyrus-based analysis or thinner foci within the gyri using vertex-based analysis. However, the locations of these findings are inconsistent across studies, and the spatial transformations required during vertex-based analysis may affect the focal...
Preprint
Full-text available
Recent studies have begun to examine the extent to which signals in the brain correspond to the underlying white matter structure by using tools from the field of graph signal processing to quantify brain function alignment to brain network topology. Here, we apply this framework for the first time towards a transdiagnostic cohort of internalizing...
Article
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Research indicates that heightened anticipatory anxiety underlies several forms of psychopathology. Anticipatory anxiety can be reliably and objectively measured in the laboratory using the No-Predictable-Unpredictable (NPU) threat paradigm. The NPU paradigm is an ideal research tool for the NIH ‘Fast-Fail’ approach of screening promising compounds...
Article
Background Knowledge of the neural mechanisms underlying increased disease burden in the anxiety disorders that is unaccounted for by individual categorical diagnoses could lead to improved clinical care. Here, we tested the utility of a joint fMRI-EEG neurobiological profile characterized by overvaluation of negative stimuli (amygdala) in combinat...
Article
Full-text available
Background Internalizing psychopathologies (IPs) are highly comorbid and exhibit substantial overlap, such as aberrant affective reactivity. Neural reactivity to emotional images, measured via the late positive potential (LPP) event‐related potential (ERP) component, has been utilized to index affective reactivity in IPs. The LPP is often examined...
Article
Self-reported histories of mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) symptoms are prevalent among post-9/11 veterans. Both are associated with subjective and often overlapping symptom complaints, but variably with objective neuropsychological test performances. These outcomes are seldom explored in relation to life...
Article
Full-text available
Introduction: Central sensitization (CS) involves dysfunctional central nervous system pain modulation resulting in heightened pain perception. Central sensitization is not commonly assessed among patients with opioid use disorder (OUD), despite the fact that pain has been implicated in the development, maintenance, and relapse of OUD and chronic...
Article
Full-text available
Background: Exposure to trauma can result in various mental health disorders including anxiety, depression, and posttraumatic stress disorder (PTSD). Although psychotherapies and pharmacotherapies exist for the treatment of these disorders, many individuals fail to receive treatment and among those who do, many remain symptomatic. Therefore, it is...
Article
The reward positivity (RewP) event-related potential is a well-validated measure of reward processing implicated in internalizing psychopathologies. The RewP is thought to reflect reward reactivity in the mesocorticolimbic system; however, it is not clear how the RewP is related to the functional connectivity of reward-related brain regions. The cu...
Article
Objective: Posttraumatic stress disorder (PTSD) and alcohol use (AU) are highly prevalent and comorbid among post-9/11 U.S. military veterans. Both issues are associated with working memory (WM) deficits, but have rarely been studied concurrently in cognitive studies of post-9/11 veterans. They also have been measured inconsistently, with variable...
Article
Full-text available
How we perceive and interpret signals from others’ behavior, known as social-emotional information processing (SEIP), is key when responding to social threat. Impulsively aggressive individuals, behaviorally, demonstrate impaired SEIP for encoding relevant social stimuli, attribution of intent of the other person in the interaction, and responding...
Article
Background Posttraumatic stress disorder (PTSD) is accompanied by disrupted cortical neuroanatomy. We investigated alteration in covariance of structural networks associated with PTSD in regions that demonstrate the case-control differences in cortical thickness (CT) and surface area (SA). Methods Neuroimaging and clinical data were aggregated fro...
Article
Full-text available
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...
Article
Full-text available
Background Emotion regulation (ER) strategies (i.e., reappraisal, suppression) and repetitive negative thinking (RNT) tendencies (i.e., brooding rumination, worry) are transdiagnostic and contribute to the maintenance of internalizing psychopathologies. Cognitive Behavioral Therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs) are both...
Article
Guided by developmental psychopathology and dual-risk frameworks, the present study examined the interplay between childhood maltreatment and maternal major depression history in relation to neural reward responsiveness in youth. The sample consisted of 96 youth (ages 9–16; M = 12.29 years, SD = 2.20; 68.8% female) drawn from a large metropolitan c...
Article
Full-text available
The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through th...
Article
Anterior cingulate cortex (ACC) response during attentional control in the context of task-irrelevant emotional faces is a promising biomarker of cognitive behavioral therapy (CBT) outcome in patients with social anxiety disorder (SAD). However, it is unclear whether this biomarker extends to major depressive disorder (MDD) and is specific to CBT o...
Article
One sex differences in the perception of emotion is that females, particularly those with high anxiety, often show heightened identification of fearful faces. To better understand the causal role of glucocorticoids in this sex difference, we examine these associations in people with HIV(PWH) where emotion perception is impaired and mental health di...
Article
Network diffusion models are a common and powerful way to study the propagation of information through a complex system and they offer straightforward approaches for studying multimodal brain network data. We developed an analytic framework to identify brain subnetworks with perturbed information diffusion capacity using the structural basis that b...
Article
Background : Individuals with intermittent explosive disorder (IED) are reported to exhibit amygdala (AMYG) hyper-activation to anger faces during functional magnetic resonance imaging (fMRI). However, it remains unknown if emotional experience is different in study participants with IED compared with healthy controls (HC). Thus, we examined the co...
Article
Background Aberrant emotion regulation has been posited as a putative endophenotype of bipolar disorder (BD). We therefore aimed to compare the neural responses during voluntary down-regulation of negative emotions in a large functional magnetic resonance imaging study of BD, patients' unaffected first-degree relatives (URs), and healthy controls (...
Article
Full-text available
Background Prior investigation of adult patients with obsessive compulsive disorder (OCD) has found greater functional connectivity within orbitofrontal–striatal–thalamic (OST) circuitry, as well as altered connectivity within and between large-scale brain networks such as the cingulo-opercular network (CON) and default mode network (DMN), relative...
Article
Early life adversity (ELA) increases the risk of problematic alcohol use and alcohol use disorder (AUD). However, it is unclear why some but not all ELA-exposed individuals develop problematic alcohol use. Research is needed to determine how this environmental risk factor interacts with underlying neurobehavioral vulnerabilities to problem alcohol...
Article
Anxiety disorders (ADs) are common and difficult to treat. While research suggests ADs are characterized by an imbalance between bottom-up and top-down attention processes and that effective treatments work by correcting this dysfunction, there is insufficient data to explain how and for whom treatments work. The late positive potential (LPP), an e...
Article
Background Resting-state graph-based network edges can be powerful tools for identification of mood disorders. We address whether these edges can be integrated with RDoC constructs, for accurate identification of mood-disorder related markers, while minimizing active symptoms of disease. Methods We compared 132 individuals with currently remitted...
Article
Full-text available
Background Rumination and worry are repetitive negative thinking (RNT) tendencies that contribute to the development and maintenance of internalizing psychopathologies. Accruing data suggest rumination and worry represent overlapping and unique transdiagnostic cognitive processes. Yet, prior neuroimaging research has mostly focused on rumination in...
Article
Poor inhibitory control and heightened feelings of stimulation after alcohol are two well-established risk factors for alcohol use disorder (AUD). Although these risk factors have traditionally been viewed as orthogonal, recent evidence suggests that the two are related and may share common neurobiological mechanisms. Here we examined the degree to...
Article
Objective We examined the impact of post-traumatic stress disorder (PTSD) on both prospective (PM) and retrospective (RM) memory performance among a cross-sectional veteran sample. Method Data from tests of PM/RM memory and PTSD, anxiety, depression and sleep disturbance symptoms were examined among a prospectively recruited sample of 26 veterans...
Article
Objective: The relative contribution of individual cognitive behavioral therapy (CBT) components to treatment outcomes for child anxiety disorders (CADs) is unclear. Recent meta-analyses suggest that exposure may be the primary active ingredient in CBT for CADs, and that relaxation may be relatively less effective. This brief report tests the hypot...
Preprint
Full-text available
Network diffusion models are a common and powerful way to study the propagation of information through a complex system, they and offer straightforward approaches for studying multimodal brain network data. We developed an analytic framework to identify brain subnetworks with impaired information diffusion capacity using the structural basis that b...
Article
Full-text available
Background Early Life Adversity (ELA) is consistently linked to chronic, treatment-resistant depression and anxiety. Selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioral therapy (CBT) represent the two first-line treatments for internalizing disorders. However, little is known about the efficacy of these therapies for individual...
Preprint
Full-text available
Introduction Cortical thickness (CT) and surface area (SA) are established biomarkers of brain pathology in posttraumatic stress disorder (PTSD). Structural covariance networks (SCN) constructed from CT and SA may represent developmental associations, or unique interactions between brain regions, possibly influenced by a common causal antecedent. T...
Article
Full-text available
Background: Anxiety is associated with aberrant patterns of cortical thickness in regions implicated in emotion regulation. However, few studies have examined cortical thickness differences between individuals with anxiety and healthy controls (HCs) across development, particularly during childhood when cortical thinning begins and anxiety risk in...
Article
Introduction Disruptions in neural measures of reward responsiveness are implicated in risk for and the development of Substance Use Disorders (SUDs) in general, but it is not clear if this is also true for Cannabis Use Disorder (CUD). To date, no studies have examined neural reward responsiveness in cannabis users using EEG. Methods Cannabis user...
Article
Background Few studies have examined how Δ9-Tetrahydrocannabinol (THC), the main psychoactive component of cannabis, impacts brain reward circuitry in humans. In this study, we examined if an acute dose of THC altered resting state functional connectivity between the striatum and prefrontal cortex among healthy young adults with limited cannabis us...
Article
Social-emotional information processing (SEIP) is critical for appropriate human interaction. It is composed of processes that underlie how we behave towards others, especially in response to adverse social threat. We conducted a study in 26 healthy participants who completed a validated Video-SEIP (V-SEIP) task in the fMRI scanning environment. Th...
Article
Trauma exposure is prevalent, associated with multiple forms of psychopathology, and thought to alter the neurobiological substrates of threat processing. The late positive potential (LPP) is an event-related potential (ERP) that may be a clinically useful probe of the neurobiology of threat processing. Despite evidence that combat-exposed veterans...
Article
Full-text available
Studies of posttraumatic stress disorder (PTSD) report volume abnormalities in multiple regions of the cerebral cortex. However, findings for many regions, particularly regions outside commonly studied emotion-related prefrontal, insular, and limbic regions, are inconsistent and tentative. Also, few studies address the possibility that PTSD abnorma...
Article
Background Alcohol use disorder (AUD) remains an unresolved source of morbidity and mortality. Psychopharmacological challenge studies and neuroimaging experiments are two methods used to identify risk of problematic substance use. The present study combined these two approaches by examining associations between self-reported stimulation, sedation,...
Article
Background Neuroimaging studies have shown variance in brain response to emotional faces predicts cognitive behavioral therapy (CBT) outcome. An important next step is to determine if individual differences in neural predictors of CBT response represent distinct patient groups. Methods In total, 90 patients with internalizing disorders completed a...
Article
Full-text available
Background Alterations in resting‐state functional connectivity (rsFC) have been reported in posttraumatic stress disorder (PTSD). Here, we examined pre‐ and post‐treatment rsFC during a randomized clinical trial to characterize alterations and examine predictors of treatment response. Methods Sixty‐four combat veterans with PTSD were randomly ass...
Article
The error‐related negativity (ERN) is an event‐related potential that reflects error monitoring. Enhanced ERN indicates sensitivity to performance errors and is a correlate of anxiety disorders. In contrast, youth with externalizing problems exhibit a reduced ERN, suggesting decreased error monitoring. Anxiety and externalizing problems commonly co...
Article
Objective: The present study explored both embedded symptom (SVT) and performance (PVT) validity test scores within a post- 9/11 veteran sample to elucidate the degree to which there is concordance between validity indicators, as well as how frequently one SVT and four PVT indicators were failed in screened mild traumatic brain injury (mTBI) and di...
Article
Full-text available
Background Posttraumatic stress disorder (PTSD) has been associated with exaggerated threat processing and deficits in emotion modulation circuitry. It remains unknown how neural circuits are associated with response to evidence‐based treatments for PTSD. Method We examined associations between PTSD symptoms and indicators of neural response in ke...
Article
Full-text available
The ENIGMA group on Generalized Anxiety Disorder (ENIGMA‐Anxiety/GAD) is part of a broader effort to investigate anxiety disorders using imaging and genetic data across multiple sites worldwide. The group is actively conducting a mega‐analysis of a large number of brain structural scans. In this process, the group was confronted with many methodolo...
Article
One well-known phenotypic risk factor for the development of alcohol use disorder is sensitivity to the rewarding effects of alcohol. In the present study, we examined whether individuals who are sensitive to alcohol reward are also sensitive to nondrug rewards, thereby reflecting a broader individual difference risk factor. Specifically, we tested...
Article
Identifying neurobehavioral correlates of suicidal ideation can help detect those most vulnerable for suicide among high-risk groups, such as those with internalizing psychopathology. Individuals with elevated sensitivity to uncertain threat (U-threat) have a strong preference for known outcomes relative to unknown outcomes and often experience hig...
Article
This study examined the impact of perceived social support on mental health and psychosocial functioning in combat veterans after military deployment, including veterans with post-traumatic stress disorder (PTSD) and veterans with comorbid PTSD and alcohol use disorder. Veterans ( n = 139; female = 23) completed self-report and clinician-administer...
Article
Structural differences in the amygdala (AMG) are implicated in anxiety and observed among individuals with generalized (GAD) and social anxiety (SAD) disorders. Findings have been mixed, perhaps because studies rarely examine differences between GAD and SAD, test comorbidity, or examine age-related differences. We tested AMG volume differences amon...
Preprint
The ENIGMA group on Generalized Anxiety Disorder (ENIGMA-Anxiety/GAD) is part of a broader effort to investigate anxiety disorders using imaging and genetic data across multiple sites worldwide. The group is actively conducting a mega-analysis of a large number of brain structural scans. In this process, the group was confronted with many methodolo...
Article
Full-text available
Rationale and objective: Poor inhibitory control is a well-established risk factor for alcohol use disorder (AUD). Similarly, greater sensitivity to the stimulant effects and less sensitivity to the sedative effects of alcohol are also strongly linked to risk for AUD. Traditionally, these two risk factors have been considered to be orthogonal, and...
Article
Posttraumatic Stress Disorder (PTSD) is a debilitating condition often associated with difficulty in emotion regulation, including reappraising negative emotions. This study assessed neural mechanisms associated with emotion regulation in veterans prior to and following treatment for PTSD. Participants with PTSD and combat exposed controls (CC) com...
Article
The internalizing psychopathologies (IP) are a highly prevalent group of disorders for which little data exists to guide treatment selection. We examine whether graph theoretical metrics from white matter connectomes may serve as biomarkers of disease and predictors of treatment response. We focus on the uncinate fasciculus subnetwork, which has be...
Article
In major depressive disorder (MDD) and remitted MDD (rMDD) alterations in cortisol and inflammation are associated with cognitive difficulties, but these relationships have not been investigated in HIV. We used secondary data from a placebo-controlled, cross-over study of cognitive performance following a probe of the hypothalamic-pituitary-adrenal...
Article
Aberrant threat reactivity has been implicated in the pathophysiology of posttraumatic stress disorder (PTSD); however, the literature on this association is mixed. One factor that may contribute to this inconsistent association is differences in severity of posttraumatic stress symptoms (PTSSs) across studies, but no studies have tested this hypot...
Chapter
Over the last few decades, the Mekong Delta Coast has undergone many physical changes that have increased its vulnerability. Issues that have grown in importance are erosion, human occupation of coastal and estuarine mangroves, decreased sediment supply by the Mekong River and subsidence due to groundwater extraction. These issues have led to the l...
Article
In the following grant report, we describe initial and planned work supported by our National Institute of Mental Health R01-funded, Research Domain Criteria (RDoc) informed project, "Dimensional Brain Behavior Predictors of CBT Outcomes in Pediatric Anxiety". This project examines response to cognitive behavioral therapy (CBT) in a large sample of...
Article
Full-text available
The popularity of network analysis in psychopathology research has increased exponentially in recent years. Yet, little research has examined the replicability of cross-sectional psychopathology network models, and those that have used single items for symptoms rather than multiitem scales. The present study therefore examined the replicability and...
Article
Structural variations of neural regions implicated in fear responses have been well documented in the pathophysiology of anxiety and may play an important role in treatment response. We examined whether gray matter volume of three neural regions supporting fear and avoidance responses [bilateral amygdala, nucleus accumbens (NAcc), and ventromedial...