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Major depressive disorder (MDD) is the most prevalent psychiatric disorder, characterized by at least one life-disrupting depressive episode and high risk for relapse after recovery (40% within 2 years). Risk for relapse and chronic-MDD increases dramatically with the number of previous episodes. Therefore, preventing relapse in the remitted phase is a major, but largely overlooked opportunity in treating MDD.


Preventive cognitive therapy (CT) in remitted-MDD has been successful in lowering relapse-risk, though not in all patients. Mechanisms underlying preventive-CT are unclear, hindering clinicians in predicting for whom pCT is warranted. Reliable predictors of preventive-treatment success are currently lacking, yet urgently needed. Clearly, accurate prediction of preventive-success contributes to effective preventive-treatment allocation and lower relapse-rates.


My approach is to use state-of-the-art neurocognitive methods in the context of a randomized controlled trial of preventive-CT in remitted-MDD to: 1) understand mechanisms of preventive-CT and 2) identify predictors of individual preventive-CT-success. I hypothesize that capacity of the brain’s prefrontal cortex to regulate emotional information is crucial for understanding and predicting pCT-success.


However, routinely performing neuroimaging investigations for predicting treatment-success is clinically not feasible. Therefore, I aim to validate the pupil dilation-response (an autonomic index previously linked to emotion regulation-success and associated brain activation) as reflector of brain-activation during emotion regulation in remitted-MDD, for use in innovative non-imaging, brain-informed prediction and monitoring of pCT-success.


Seventy-five remitted MDD-patients are randomized to pCT (8 weeks;n=50) or no treatment (n=25). Pre- and post-treatment I will measure emotional control, using functional magnetic resonance imaging (MRI) with simultaneous pupil-recordings in all patients. Furthermore, 25 healthy controls are included to establish residual abnormalities in emotional control.


This research substantially contributes to understanding neurocognitive mechanisms underlying relapse and relapse-prevention in MDD. Translating neuroimaging research for applications in clinical practice denotes a major step forward in preventing relapse for individual patients.


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