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Modeling anxiety in healthy humans: a key intermediate bridge between basic and clinical sciences

Grillon, C; Robinson, OJ; Cornwell, B; Ernst, M; (2019) Modeling anxiety in healthy humans: a key intermediate bridge between basic and clinical sciences. Neuropsychopharmacology , 44 pp. 1999-2010. 10.1038/s41386-019-0445-1. Green open access

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Abstract

Animal models of anxiety disorders are important for elucidating neurobiological defense mechanisms. However, animal models are limited when it comes to understanding the more complex processes of anxiety that are unique to humans (e.g., worry) and to screen new treatments. In this review, we outline how the Experimental Psychopathology approach, based on experimental models of anxiety in healthy subjects, can mitigate these limitations and complement research in animals. Experimental psychopathology can bridge basic research in animals and clinical studies, as well as guide and constrain hypotheses about the nature of psychopathology, treatment mechanisms, and treatment targets. This review begins with a brief review of the strengths and limitations of animal models before discussing the need for human models of anxiety, which are especially necessary to probe higher-order cognitive processes. This can be accomplished by combining anxiety-induction procedures with tasks that probe clinically relevant processes to identify neurocircuits that are potentially altered by anxiety. The review then discusses the validity of experimental psychopathology and introduces a methodological approach consisting of five steps: (1) select anxiety-relevant cognitive or behavioral operations and associated tasks, (2) identify the underlying neurocircuits supporting these operations in healthy controls, 3) examine the impact of experimental anxiety on the targeted operations in healthy controls, (4) utilize findings from step 3 to generate hypotheses about neurocircuit dysfunction in anxious patients, and 5) evaluate treatment mechanisms and screen novel treatments. This is followed by two concrete illustrations of this approach and suggestions for future studies.

Type: Article
Title: Modeling anxiety in healthy humans: a key intermediate bridge between basic and clinical sciences
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41386-019-0445-1
Publisher version: https://doi.org/10.1038/s41386-019-0445-1
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Cognitive control, Experimental models of disease, Prefrontal cortex
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences > Institute of Cognitive Neuroscience
URI: https://discovery.ucl.ac.uk/id/eprint/10077471
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