Browsing by Subject "Anxiety disorders"

Now showing 1 - 9 of 9
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    A randomized proof-of-mechanism trial applying the 'fast-fail' approach to evaluating κ-opioid antagonism as a treatment for anhedonia
    (Springer Nature, 2020) Krystal, Andrew D.; Pizzagalli, Diego A.; Smoski, Moria; Mathew, Sanjay J.; Nurnberger, John, Jr.; Lisanby, Sarah H.; Iosifescu, Dan; Murrough, James W.; Yang, Hongqiu; Weiner, Richard D.; Calabrese, Joseph R.; Sanacora, Gerard; Hermes, Gretchen; Keefe, Richard S. E.; Song, Allen; Goodman, Wayne; Szabo, Steven T.; Whitton, Alexis E.; Gao, Keming; Potter, William Z.; Psychiatry, School of Medicine
    The National Institute of Mental Health (NIMH) 'fast-fail' approach seeks to improve too-often-misleading early-phase drug development methods by incorporating biomarker-based proof-of-mechanism (POM) testing in phase 2a. This first comprehensive application of the fast-fail approach evaluated the potential of κ-opioid receptor (KOR) antagonism for treating anhedonia with a POM study determining whether robust target engagement favorably impacts the brain circuitry hypothesized to mediate clinical effects. Here we report the results from a multicenter, 8-week, double-blind, placebo-controlled, randomized trial in patients with anhedonia and a mood or anxiety disorder (selective KOR antagonist (JNJ-67953964, 10 mg; n = 45) and placebo (n = 44)). JNJ-67953964 significantly increased functional magnetic resonance imaging (fMRI) ventral striatum activation during reward anticipation (primary outcome) as compared to placebo (baseline-adjusted mean: JNJ-67953964, 0.72 (s.d. = 0.67); placebo, 0.33 (s.d. = 0.68); F(1,86) = 5.58, P < 0.01; effect size = 0.58 (95% confidence interval, 0.13-0.99)). JNJ-67953964, generally well tolerated, was not associated with any serious adverse events. This study supports proceeding with assessment of the clinical impact of target engagement and serves as a model for implementing the 'fast-fail' approach.
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    Attachment Avoidance and Depressive Symptoms: A Test of Moderation by Cognitive Abilities
    (2014-09-04) Shea, Amanda Marie; Rand, Kevin L.; Stewart, Jesse C.; Cyders, Melissa A.; Ashburn-Nardo, Leslie; Grahame, Nicholas J.
    The substantial interpersonal and economic costs of depression make it imperative to better understand the predictors and moderators of depressive symptoms. The ability to use social support protects people from depressive symptoms, but individuals high in attachment avoidance tend not to use others as sources of support. Research has found that attachment avoidance is related to depressive symptoms in some samples but not in others (Mikulincer & Shaver, 2007; Shea, 2011). Thus, there appear to be factors that moderate the relationship between attachment avoidance and depressive symptoms. The present study examined if cognitive abilities that facilitate effective emotion regulation strategies moderate the relationship between attachment avoidance and depressive symptoms. Using a sample of college students, attachment avoidance, cognitive abilities, depressive symptoms, and other indices of psychological distress and well-being were measured and examined for evidence of moderation via hierarchical linear regression. The hypothesis that cognitive abilities moderate the relationship between attachment avoidance and depressive symptoms was not supported (ΔR2 = 0.02, p = .68). Factors contributing to the null findings are discussed and conceptual and methodological suggestions are offered for future research.
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    Correction to: Selective kappa-opioid antagonism ameliorates anhedonic behavior: evidence from the Fast-fail Trial in Mood and Anxiety Spectrum Disorders (FAST-MAS)
    (Springer Nature, 2021) Pizzagalli, Diego A.; Smoski, Moria; Ang, Yuen-Siang; Whitton, Alexis E.; Sanacora, Gerard; Mathew, Sanjay J.; Nurnberger, John, Jr.; Lisanby, Sarah H.; Iosifescu, Dan V.; Murrough, James W.; Yang, Hongqiu; Weiner, Richard D.; Calabrese, Joseph R.; Goodman, Wayne; Potter, William Z.; Krystal, Andrew D.; Psychiatry, School of Medicine
    Correction to: Neuropsychopharmacology 10.1038/s41386-020-0738-4, published online 16 June 2020 In this article a conflict of interest was missing. The co-author Sanjay J. Mathew served as a consultant to Alkermes. The original article has been corrected. The original article can be found online at 10.1038/s41386-020-0738-4.
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    Olfactory Reference Syndrome: A Case Report and Screening Tool
    (Springer, 2020-04) Chernyak, Yelena; Chapleau, Kristine M.; Tanious, Shariff F.; Dattilo, Natalie C.; Diaz, David R.; Landsberger, Sarah A.
    Olfactory reference syndrome (ORS) is a lesser known disorder that is related to obsessive–compulsive disorder. ORS is the obsessional and inaccurate belief that one is emitting a foul odor leading to embarrassment or concern about offending others, excessive hygiene behaviors, and social avoidance that significantly interferes with daily functioning. Although ORS is rare, it is challenging to diagnose. ORS-sufferers first seek treatment from non- psychiatric providers (e.g., dermatologists, dentists.) to alleviate the perceived odor, which frequently leads to misdiagnosis and unnecessary treatments. Additionally, because ORS-sufferers can have limited insight and ideas of reference, they can be misdiagnosed as having a psychotic or delusional disorder. We present a case report of a 42-year-old woman with ORS, and how the correct diagnosis of ORS provided with psychiatric treatment led to significant improvement in her daily functioning. We provide a literature review on the disorder as well as a short screener to assess ORS.
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    Patient Health Questionnaire Anxiety and Depression Scale: Initial Validation in Three Clinical Trials
    (Wolters Kluwer, 2016-07) Kroenke, Kurt; Wu, Jingwei; Yu, Zhangsheng; Bair, Matthew J.; Kean, Jacob; Stump, Timothy; Monahan, Patrick O.; Medicine, School of Medicine
    OBJECTIVE: We examine the reliability and validity of the Patient Health Questionnaire Anxiety and Depression Scale (PHQ-ADS)-which combines the nine-item Patient Health Questionnaire depression scale and seven-item Generalized Anxiety Disorder scale-as a composite measure of depression and anxiety. METHODS: Baseline data from 896 patients enrolled in two primary-care based trials of chronic pain and one oncology-practice-based trial of depression and pain were analyzed. The internal reliability, standard error of measurement, and convergent, construct, and factor structure validity, as well as sensitivity to change of the PHQ-ADS were examined. RESULTS: The PHQ-ADS demonstrated high internal reliability (Cronbach α values of .8 to .9) in all three trials. PHQ-ADS scores can range from 0 to 48 (with higher scores indicating more severe depression/anxiety), and the estimated standard error of measurement was approximately 3 to 4 points. The PHQ-ADS showed strong convergent (most correlations, 0.7-0.8 range) and construct (most correlations, 0.4-0.6 range) validity when examining its association with other mental health, quality of life, and disability measures. PHQ-ADS cutpoints of 10, 20, and 30 indicated mild, moderate, and severe levels of depression/anxiety, respectively. Bifactor analysis showed sufficient unidimensionality of the PHQ-ADS score. PHQ-ADS change scores at 3 months differentiated (p < .0001) between individuals classified as worse, stable, or improved by a reference measure, providing preliminary evidence for sensitivity to change. CONCLUSIONS: The PHQ-ADS may be a reliable and valid composite measure of depression and anxiety which, if validated in other populations, could be useful as a single measure for jointly assessing two of the most common psychological conditions in clinical practice and research.
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    Pilot Study of Self-Distancing Augmentation to Exposure Therapy for Youth Anxiety
    (Springer Nature, 2023-05-26) Bilek, Emily L.; Meyer, Allison E.; Tomlinson, Rachel; Chen, Carol; Psychiatry, School of Medicine
    This pilot examines a self-distancing augmentation to exposure. Nine youth with anxiety (ages 11-17; 67% female) completed treatment. The study employed a brief (eight session) crossover ABA/BAB design. Exposure difficulty, engagement with exposure, and treatment acceptability were examined as primary outcome variables. Visual inspection of plots indicated that youth completed more difficult exposures during augmented exposure sessions [EXSD] than classic exposure sessions [EX] by therapist- and youth-report and that therapists reported higher youth engagement during EXSD than EX sessions. There were no significant differences between EXSD and EX on exposure difficulty or engagement by therapist- or youth-report. Treatment acceptability was high, although some youth reported that self-distancing was "awkward". Self-distancing may be associated with increased exposure engagement and willingness to complete more difficult exposures, which has been linked to treatment outcomes. Future research is needed to further demonstrate this link, and link self-distancing to outcomes directly.
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    Reduced top‐down attentional control in adolescents with generalized anxiety disorder
    (Wiley, 2021) Bashford-Largo, Johannah; Aloi, Joseph; Lukoff, Jennie; Johnson, Kimberly; White, Stuart F.; Dobbertin, Matthew; Blair, Robert James; Blair, Karina S.; Psychiatry, School of Medicine
    Background: Generalized anxiety disorder (GAD) can significantly impair quality of life and is associated with a relatively poor long-term prognosis. Anxiety disorders are often associated with hyper-responsiveness to threat, perhaps coupled with impaired executive functioning. However, GAD, particularly adolescent GAD, has been the focus of little functional neuroimaging work compared to other anxiety disorders. Here, we examine the neural association of adolescent GAD with responsiveness to threat and response control. Methods: The study involved 35 adolescents with GAD and 34 healthy comparison individuals (N = 69) matched on age, gender, and IQ. Participants were scanned during an affective number Stroop task. Results: We found significant Group-by-Task Condition interactions in regions involved in response control/motor responding (bilateral precentral gyri and cerebellum) and/or cognitive control/attention (dorsomedial and lateral frontal cortex, posterior cingulate cortex, cuneus, and precuneus). In line with predictions, the youth with GAD showed significantly less recruitment during task trials than the healthy comparison individuals. However, no indications of specific heightened responses to threat were seen. Conclusions: GAD involves reduced capacity for engaging regions involved in response control/motor responding and/or cognitive control/attention. This might reflect either a secondary consequence of the patient's worry or an early risk factor for the development of worry.
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    Towards precision medicine for anxiety disorders: objective assessment, risk prediction, pharmacogenomics, and repurposed drugs
    (Springer Nature, 2023) Roseberry, K.; Le-Niculescu, H.; Levey, D. F.; Bhagar, R.; Soe, K.; Rogers, J.; Palkowitz, S.; Pina, N.; Anastasiadis, W. A.; Gill, S. S.; Kurian, S. M.; Shekhar, A.; Niculescu, A. B.; Psychiatry, School of Medicine
    Anxiety disorders are increasingly prevalent, affect people's ability to do things, and decrease quality of life. Due to lack of objective tests, they are underdiagnosed and sub-optimally treated, resulting in adverse life events and/or addictions. We endeavored to discover blood biomarkers for anxiety, using a four-step approach. First, we used a longitudinal within-subject design in individuals with psychiatric disorders to discover blood gene expression changes between self-reported low anxiety and high anxiety states. Second, we prioritized the list of candidate biomarkers with a Convergent Functional Genomics approach using other evidence in the field. Third, we validated our top biomarkers from discovery and prioritization in an independent cohort of psychiatric subjects with clinically severe anxiety. Fourth, we tested these candidate biomarkers for clinical utility, i.e. ability to predict anxiety severity state, and future clinical worsening (hospitalizations with anxiety as a contributory cause), in another independent cohort of psychiatric subjects. We showed increased accuracy of individual biomarkers with a personalized approach, by gender and diagnosis, particularly in women. The biomarkers with the best overall evidence were GAD1, NTRK3, ADRA2A, FZD10, GRK4, and SLC6A4. Finally, we identified which of our biomarkers are targets of existing drugs (such as a valproate, omega-3 fatty acids, fluoxetine, lithium, sertraline, benzodiazepines, and ketamine), and thus can be used to match patients to medications and measure response to treatment. We also used our biomarker gene expression signature to identify drugs that could be repurposed for treating anxiety, such as estradiol, pirenperone, loperamide, and disopyramide. Given the detrimental impact of untreated anxiety, the current lack of objective measures to guide treatment, and the addiction potential of existing benzodiazepines-based anxiety medications, there is a urgent need for more precise and personalized approaches like the one we developed.
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    Use of serial smartphone-based assessments to characterize diverse neuropsychiatric symptom trajectories in a large trauma survivor cohort
    (Springer Nature, 2023-01-07) Beaudoin, Francesca L.; An, Xinming; Basu, Archana; Ji, Yinyao; Liu, Mochuan; Kessler, Ronald C.; Doughtery, Robert F.; Zeng, Donglin; Bollen, Kenneth A.; House, Stacey L.; Stevens, Jennifer S.; Neylan, Thomas C.; Clifford, Gari D.; Jovanovic, Tanja; Linnstaedt, Sarah D.; Germine, Laura T.; Rauch, Scott L.; Haran, John P.; Storrow, Alan B.; Lewandowski, Christopher; Musey, Paul I., Jr.; Hendry, Phyllis L.; Sheikh, Sophia; Jones, Christopher W.; Punches, Brittany E.; Kurz, Michael C.; Swor, Robert A.; Murty, Vishnu P.; McGrath, Meghan E.; Hudak, Lauren A.; Pascual, Jose L.; Datner, Elizabeth M.; Chang, Anna M.; Pearson, Claire; Peak, David A.; Merchant, Roland C.; Domeier, Robert M.; Rathlev, Niels K.; O' Neil, Brian J.; Sergot, Paulina; Sanchez, Leon D.; Bruce, Steven E.; Baker, Justin T.; Joormann, Jutta; Miller, Mark W.; Pietrzak, Robert H.; Barch, Deanna M.; Pizzagalli, Diego A.; Sheridan, John F.; Smoller, Jordan W.; Harte, Steven E.; Elliott, James M.; Koenen, Karestan C.; Ressler, Kerry J.; McLean, Samuel A.; Emergency Medicine, School of Medicine
    The authors sought to characterize adverse posttraumatic neuropsychiatric sequelae (APNS) symptom trajectories across ten symptom domains (pain, depression, sleep, nightmares, avoidance, re-experiencing, anxiety, hyperarousal, somatic, and mental/fatigue symptoms) in a large, diverse, understudied sample of motor vehicle collision (MVC) survivors. More than two thousand MVC survivors were enrolled in the emergency department (ED) and completed a rotating battery of brief smartphone-based surveys over a 2-month period. Measurement models developed from survey item responses were used in latent growth curve/mixture modeling to characterize homogeneous symptom trajectories. Associations between individual trajectories and pre-trauma and peritraumatic characteristics and traditional outcomes were compared, along with associations within and between trajectories. APNS across all ten symptom domains were common in the first two months after trauma. Many risk factors and associations with high symptom burden trajectories were shared across domains. Both across and within traditional diagnostic boundaries, APNS trajectory intercepts, and slopes were substantially correlated. Across all domains, symptom severity in the immediate aftermath of trauma (trajectory intercepts) had the greatest influence on the outcome. An interactive data visualization tool was developed to allow readers to explore relationships of interest between individual characteristics, symptom trajectories, and traditional outcomes ( http://itr.med.unc.edu/aurora/parcoord/ ). Individuals presenting to the ED after MVC commonly experience a broad constellation of adverse posttraumatic symptoms. Many risk factors for diverse APNS are shared. Individuals diagnosed with a single traditional outcome should be screened for others. The utility of multidimensional categorizations that characterize individuals across traditional diagnostic domains should be explored.