Anxiety is an adaptive response that promotes harm avoidance, but at the same time excessive anxiety constitutes the most common psychiatric complaint. Moreover, current treatments for anxiety—both psychological and pharmacological—hover at around 50% recovery rates. Improving treatment outcomes is nevertheless difficult, in part because contemporary interventions were developed without an understanding of the underlying neurobiological mechanisms that they modulate. Recent advances in experimental models of anxiety in humans, such as threat of unpredictable shock, have, however, enabled us to start translating the wealth of mechanistic animal work on defensive behaviour into humans. In this article, we discuss the distinction between fear and anxiety, before reviewing translational research on the neural circuitry of anxiety in animal models and how it relates to human neuroimaging studies across both healthy and clinical populations. We highlight the roles of subcortical regions (and their subunits) such as the bed nucleus of the stria terminalis, the amgydala, and the hippocampus, as well as their connectivity to cortical regions such as dorsal medial and lateral prefrontal/cingulate cortex and insula in maintaining anxiety responding. We discuss how this circuitry might be modulated by current treatments before finally highlighting areas for future research that might ultimately improve treatment outcomes for this common and debilitating transdiagnostic symptom.
- psychology, experimental
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Contributors OJR, ACP, BC and CG are all responsible for drafting and editing this manuscript.
Funding This work was supported by the personal fellowships MR/K024280/1 and MR/R020817/1 from the Medical Research Council to OJR and the Intramural Research Program of the National Institute of Mental Health, project number ZIAMH002798 (clinical protocol 02-M-0321 (NCT00047853), 01-M-0185 (NCT00026559)) to CG. OJR has completed consultancy work for IESO digital health and Brainbow and is running an Investigator Initiated Trial with Lundbeck. He holds an MRC Industrial Collaboration Award with Cambridge Cognition.
Competing interests OJR has completed consultancy work for Ieso Digital Health and Brainbow and is running an Investigator Initiated Trial with Lundbeck. He holds an MRC Industrial Collaboration Award with Cambridge Cognition.
Patient consent for publication Not required.
Provenance and peer review Commissioned; internally peer reviewed.
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