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Cognitive bias modification for emotional facial expressions modifies neural mechanisms in individuals taking antidepressant medication: a Randomised Controlled Trial

Crisp, C. M.; Fallon, S. J.; Burns, A.; Kuruoglu, R.; Ferrar, J.; Wiles, N.; Kessler, D.; Munafo, M. R.; Penton-Voak, I. S.

2026-02-03 psychiatry and clinical psychology
10.64898/2026.01.27.26344720 medRxiv
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BackgroundAntidepressants exert their therapeutic effects through ameliorating negative emotional biases that underpin depression. However, therapeutic gains may depend upon restructuring how emotional information is processed. This can be achieved through Cognitive Bias Modification (CBM), a technique for positively shifting recognition of emotional facial expressions. Here, we examined how CBM modifies emotional processing circuits in individuals with depression who were taking Selective Serotonin Reuptake Inhibitors (SSRIs). MethodsA double-blind Randomised Controlled Trial was conducted in 84 participants with depression who had recently started SSRI medication. Participants received five sessions of active or sham CBM over one week before fMRI scanning where they viewed emotional faces (happy, fearful, sad). ResultsAcross all emotional expressions, greater Blood Oxygen Level Dependent (BOLD) signal was observed in the inferior occipital gyrus for the active compared to sham CBM. Emotional-specific effects were observed in the medial Prefrontal Cortex (mPFC), with reduced BOLD signal in the active (compared to sham) group for viewing happy vs. fearful faces. Changes in BOLD signal were also associated with individual differences in response to CBM. Enhanced functional connectivity between mPFC and right Dorsolateral Prefrontal Cortex (rDLPFC) predicted improvement in depressive symptoms four weeks later. ConclusionsThese results indicate that CBM modifies the neural circuits involved in emotion processing in people with depression currently taking antidepressants. Converting these changes in emotional perception to improved depressive symptoms was related to changing mPFC-rDLPFC connectivity. Future trials are needed to test CBMs clinical utility as a simple, affordable and accessible adjunct therapy for depression.

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