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Associations between aversive learning processes and transdiagnostic psychiatric symptoms revealed by large-scale phenotyping

Wise, Toby and Dolan, Raymond J. (2019) Associations between aversive learning processes and transdiagnostic psychiatric symptoms revealed by large-scale phenotyping. . (Unpublished)

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Background: Aversive learning processes are a candidate source of dysfunction in psychiatric disorders. Here symptom expression in a range of conditions is linked to altered threat perception, manifesting particularly in uncertain environments. How precise computational mechanisms that support aversive learning, and uncertainty estimation, relate to the presence of specific psychiatric symptoms remains undetermined. Methods: 400 subjects completed a novel online game-based aversive learning task, requiring avoidance of negative outcomes, in conjunction with completing measures of common psychiatric symptoms. We used a probabilistic computational model to measure distinct processes involved in learning, in addition to inferred estimates of safety likelihood and uncertainty. We tested for associations between learning processes and traditional psychiatric constructs alongside transdiagnostic factors using linear models. We used partial least squares regression to identify components of psychopathology grounded in both aversive learning behaviour and symptom self-report. Results: State anxiety and a transdiagnostic compulsivity-related factor were associated with enhanced learning from safety. However, data-driven analysis using partial least squares regression indicated the presence of two separable components across our behavioural and questionnaire data: one linked enhanced safety learning and lower estimated uncertainty to physiological anxiety, compulsivity, and impulsivity; the other linked enhanced threat learning and heightened uncertainty estimation to symptoms of depression and social anxiety. Conclusions: Our findings implicate aversive learning processes under uncertainty to the expression of psychiatric symptoms that cut across traditional diagnostic boundaries. These relationships are more complex than previously conceptualised. Future research should focus on understanding the neural mechanisms underlying alterations in aversive learning and how these lead to the development of symptoms and disorder.

Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription Paper ItemData/Code
Wise, Toby0000-0002-9021-3282
Dolan, Raymond J.0000-0001-9356-761X
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. bioRxiv preprint first posted online Nov. 15, 2019. T.W. is supported by a Wellcome Trust Sir Henry Wellcome Fellowship (206460/17/Z). R.J.D. holds a Wellcome Trust Investigator award (098362/Z/12/Z). The Max Planck UCL Centre is a joint initiative supported by UCL and the Max Planck Society. The Wellcome Centre for Human Neuroimaging is supported by core funding from the Wellcome Trust (203147/Z/16/Z). We thank Evan Russek for comments on an earlier version of this manuscript.
Funding AgencyGrant Number
Wellcome Trust206460/17/Z
Wellcome Trust098362/Z/12/Z
Max Planck SocietyUNSPECIFIED
Wellcome Trust203147/Z/16/Z
Record Number:CaltechAUTHORS:20191118-093953938
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Official Citation:Associations between aversive learning processes and transdiagnostic psychiatric symptoms revealed by large-scale phenotyping. Toby Wise, Raymond J Dolan. bioRxiv 843045; doi:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:99893
Deposited By: Tony Diaz
Deposited On:18 Nov 2019 17:52
Last Modified:25 Nov 2020 00:31

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