Behavioral Correlates of Anxiety

Article (PDF Available)inCurrent Topics in Behavioral Neurosciences 2(2):205-28 · January 2010with690 Reads
DOI: 10.1007/7854_2009_11 · Source: PubMed
The tripartite model of anxiety includes three response domains: cognitive (most often identified by self report), behavioral, and physiological. Each is suggested to bring a separate element of response characteristics and, in some cases, potentially independent underlying mechanisms to the construct of anxiety. In this chapter, commonly used behavioral correlates of anxiety in human research, including startle reflex, attentional bias, and avoidance tasks, as well as future tasks using virtual reality technology will be discussed. The focus will be in evaluating their translational utility supported by (1) convergent validity with other measures of anxiety traits or anxiety disorders, (2) their use in identifying neural and genetic mechanisms of anxiety, and (3) ability to predict treatment efficacy.

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Available from: Victoria B Risbrough
    • "Development of laboratory-based behavioral measures of disease-related processes is a critical component of the evolution of translational research (Bowers and Ressler 2015). These tasks can bridge complex clinical presentations with discrete biological mechanisms (Braff 2015; Gottesman and Gould 2003; Rasetti and Weinberger 2011; Risbrough 2010). This strategy is now endorsed by the Research Domain Criteria (RDoC) project by the National Institute for Mental Health (Cuthbert and Insel 2013). "
    [Show abstract] [Hide abstract] ABSTRACT: The use of quantitative, laboratory-based measures of threat in humans for proof-of-concept studies and target development for novel drug discovery has grown tremendously in the last 2 decades. In particular, in the field of posttraumatic stress disorder (PTSD), human models of fear conditioning have been critical in shaping our theoretical understanding of fear processes and importantly, validating findings from animal models of the neural substrates and signaling pathways required for these complex processes. Here, we will review the use of laboratory-based measures of fear processes in humans including cued and contextual conditioning, generalization, extinction, reconsolidation, and reinstatement to develop novel drug treatments for PTSD. We will primarily focus on recent advances in using behavioral and physiological measures of fear, discussing their sensitivity as biobehavioral markers of PTSD symptoms, their response to known and novel PTSD treatments, and in the case of d-cycloserine, how well these findings have translated to outcomes in clinical trials. We will highlight some gaps in the literature and needs for future research, discuss benefits and limitations of these outcome measures in designing proof-of-concept trials, and offer practical guidelines on design and interpretation when using these fear models for drug discovery.
    Full-text · Article · Jun 2016
    • "Paralleling the findings for brain imaging of neural circuits, a wide range of disorders share common symptoms. For example, multiple anxiety disorders (e.g., specific phobia, panic and social anxiety) share symptoms of anxious arousal (implicating dysfunctions in bottom-up threat reactivity), while other general and trauma-related anxiety disorders (GAD and PTSD) are accompanied by more cognitive experiences of anxiety, such as apprehensive expectations (implicating lack of emotion regulation) [40, 41]. Data-driven techniques such as factor analysis may be useful in identifying specific dimensions of symptoms that cut across traditional diagnoses [42]. "
    [Show abstract] [Hide abstract] ABSTRACT: Background Understanding how brain circuit dysfunctions relate to specific symptoms offers promise for developing a brain-based taxonomy for classifying psychopathology, identifying targets for mechanistic studies and ultimately for guiding treatment choice. The goal of the Research Domain Criteria (RDoC) initiative of the National Institute of Mental Health is to accelerate the development of such neurobiological models of mental disorder independent of traditional diagnostic criteria. In our RDoC Anxiety and Depression (“RAD”) project we focus trans-diagnostically on the spectrum of depression and anxiety psychopathology. Our aims are a) to use brain imaging to define cohesive dimensions defined by dysfunction of circuits involved in reactivity to and regulation of negatively valenced emotional stimulation and in cognitive control, b) to assess the relationships between these dimension and specific symptoms, behavioral performance and the real world capacity to function socially and at work and c) to assess the stability of brain-symptom-behavior-function relationships over time. Methods and design Here we present the protocol for the “RAD” project, one of the first RDoC studies to use brain circuit functioning to define new dimensions of psychopathology. The RAD project follows baseline-follow up design. In line with RDoC principles we use a strategy for recruiting all clients who “walk through the door” of a large community mental health clinic as well as the surrounding community. The clinic attends to a broad spectrum of anxiety and mood-related symptoms. Participants are unmedicated and studied at baseline using a standardized battery of functional brain imaging, structural brain imaging and behavioral probes that assay constructs of threat reactivity, threat regulation and cognitive control. The battery also includes self-report measures of anxiety and mood symptoms, and social and occupational functioning. After baseline assessments, therapists in the clinic apply treatment planning as usual. Follow-up assessments are undertaken at 3 months, to establish the reliability of brain–based subgroups over time and to assess whether these subgroups predict real–world functional capacity over time. First enrollment was August 2013, and is ongoing. Discussion This project is designed to advance knowledge toward a neural circuit taxonomy for mental disorder. Data will be shared via the RDoC database for dissemination to the scientific community. The clinical translational neuroscience goals of the project are to develop brain-behavior profile reports for each individual participant and to refine these reports with therapist feedback. Reporting of results is expected from December 2016 onward. Trial registration Identifier: NCT02220309. Registered: August 13, 2014.
    Full-text · Article · Mar 2016
    • "It is well documented that startle reactivity is increased during presentation of unconditioned (e.g., foot shock) and conditioned (e.g., shockpaired cue light) aversive stimuli (Davis et al., 1989 ), or after presentation of more ethologically threatening stimuli (e.g., bright light for rodents) (Walker and Davis, 1997b). These startle-based tests provide translational measures for evaluating the potential efficacy of putative anxiolytic compounds because startle reactivity is a cross-species defensive behavior (Risbrough, 2010). These tests allow for a direct comparison of anxiety-like effects across both unconditioned and conditioned anxiety states. "
    [Show abstract] [Hide abstract] ABSTRACT: GABAB (γ-aminobutyric acid B) receptors may be a therapeutic target for anxiety disorders. Here we characterized the effects of the GABAB receptor positive allosteric modulator (PAM) BHF177 on conditioned and unconditioned physiological responses to threat in the light-enhanced startle (LES), stress-induced hyperthermia, and fear-potentiated startle (FPS) procedures in rats. The effects of BHF177 on LES were compared with those of the GABAB receptor agonists baclofen and CGP44532, and the positive control buspirone, a 5-HT1A receptor partial agonist with anxiolytic activity in humans. Baclofen (0.4, 0.9 and 1.25 mg/kg) and CGP44532 (0.065, 0.125 and 0.25 mg/kg) administration had significant sedative, but not anxiolytic, activity reflected in overall decrease in the startle response in the LES tests. BHF177 (10, 20 and 40 mg/kg) had no effect on LES, nor did it produce an overall sedative effect. Interesting, however, when rats were grouped by high and low LES responses, BHF177 had anxiolytic-like effects only on LES in high, but not low, LES responding rats. BHF177 also blocked stress-induced hyperthermia, but had no effect on conditioned fear responses in the FPS test. Buspirone (1 and 3 mg/kg) had an anxiolytic-like profile in both LES and FPS tests. These results indicate that BHF177 may specifically attenuate unconditioned anxiety in individuals that exhibit a high anxiety state, and has fewer sedative effects than direct agonists. Thus, BHF177 or other GABAB receptor PAMs may be promising compounds for alleviating increased anxiety seen in various psychiatric disorders with a superior side-effect profile compared to GABAB receptor agonists. Published by Elsevier Ltd.
    Article · May 2015
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