Reward-related activation of fronto-striatal regions scaled negatively with C-reactive protein

Aruldass, Athina R., Kitzbichler, Manfred, Lim, Tsen Vei, Wellcome Trust Consortium for Neuroimmunology of Mood Disorders, Cavanagh, Jonathan, Cowen, Philip, Pariante, Carmine, Bullmore, Edward and Harrison, Neil ORCID: https://orcid.org/0000-0002-9584-3769 2025. Reward-related activation of fronto-striatal regions scaled negatively with C-reactive protein. Psychological Medicine 55 , e308. 10.1017/s0033291725102031

PDF - Published Version Available under License Creative Commons Attribution. Download (1MB)

Abstract

Background: Depression is characterized by divergent changes in positive and negative affect. Emerging roles of inflammation in depression portend avenues for novel immunomodulator-based monotherapy, targeting mechanistically distinct symptoms such as anhedonia and pessimism. Methods: To investigate links between these divergent affective components and inflammation, we used a probabilistic reinforcement-learning fMRI paradigm, testing for evidence of hyposensitivity to reward, and hypersensitivity to punishment in low-inflammation depression cases (loCRP depression; CRP ≤ 3 mg/L; N = 48), high-inflammation depression cases (hiCRP depression; CRP > 3 mg/L; N = 31), and healthy controls (HC; CRP ≤ 3 mg/L; N = 45). We aimed to (i) determine whether depression cases with high and low inflammation showed aberrant neural activation to monetary gains and losses compared to controls, and (ii) examine if these alterations correlated with a continuous measure of C-reactive protein (CRP) in depression, as well as indices of anhedonia and pessimism derived from behavioral instruments in depression. Results: Voxel-wise activation was observed in key brain regions sensitive to monetary reward (ventromedial prefrontal cortex, vmPFC; nucleus accumbens, NAc) and punishment (insula) outcomes across all three groups. However, there was no significant difference in activation between groups. Within depression cases, increasing CRP scaled negatively with activation in the right vmPFC and left NAc but not insula cortex. However, there was no significant association between regional activation and severity of anhedonia or pessimism. Conclusions: Our results support the previously reported association between CRP and striatal reward reactivity in depression but do not extend this to processing of negatively valenced information.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Schools > Psychology Research Institutes & Centres > Cardiff University Brain Research Imaging Centre (CUBRIC)
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by-nc-nd/4.0, Type: open-access
Publisher:	Cambridge University Press
ISSN:	0033-2917
Date of First Compliant Deposit:	15 October 2025
Date of Acceptance:	15 September 2025
Last Modified:	15 Oct 2025 10:45
URI:	https://orca.cardiff.ac.uk/id/eprint/181682

Actions (repository staff only)

Edit Item