1. Neural circuit basis of pathological anxiety.
- Author
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Akiki TJ, Jubeir J, Bertrand C, Tozzi L, and Williams LM
- Subjects
- Humans, Animals, Neural Pathways physiopathology, Anxiety physiopathology, Nerve Net physiopathology, Nerve Net diagnostic imaging, Nerve Net pathology, Anxiety Disorders physiopathology, Anxiety Disorders pathology, Brain physiopathology, Brain pathology
- Abstract
Anxiety disorders are the most prevalent mental health conditions worldwide. Unfortunately, the understanding of the precise neurobiological mechanisms that underlie these disorders remains limited. Current diagnostic classifications, based on observable symptoms rather than underlying pathophysiology, do not capture the heterogeneity within and across anxiety disorders. Recent advances in functional neuroimaging have provided new insights into the neural circuits implicated in pathological anxiety, revealing dysfunctions that cut across traditional diagnostic boundaries. In this Review, we synthesize evidence that highlights abnormalities in neurobehavioural systems related to negative valence, positive valence, cognitive systems and social processes. We emphasize that pathological anxiety arises not only from heightened reactivity in acute threat ('fear') circuits but also from alterations in circuits that mediate distant (potential) and sustained threat, reward processing, cognitive control and social processing. We discuss how circuit vulnerabilities can lead to the emergence and maintenance of pathological anxiety. Once established, these neural abnormalities can be exacerbated by maladaptive behaviours that prevent extinction learning and perpetuate anxiety disorders. By delineating the specific neural mechanisms in each neurobiological system, we aim to contribute to a more comprehensive understanding of the neurobiology of anxiety disorders, potentially informing future research directions in this field., Competing Interests: Competing interests: L.M.W. declares US Patent Applications 10/034,645 and 15/820,338: ‘Systems and methods for detecting complex networks in MRI image data’. T.J.A. serves on the scientific advisory board of and has stock options with Mindbloom, and receives payment for editorial work from Elsevier. L.T. is employed by Ceribell Inc. The remaining authors declare no competing interests., (© 2024. Springer Nature Limited.)
- Published
- 2025
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