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, 19 (1), 409

Neurocognitive Working Mechanisms of the Prevention of Relapse in Remitted Recurrent Depression (NEWPRIDE): Protocol of a Randomized Controlled Neuroimaging Trial of Preventive Cognitive Therapy


Neurocognitive Working Mechanisms of the Prevention of Relapse in Remitted Recurrent Depression (NEWPRIDE): Protocol of a Randomized Controlled Neuroimaging Trial of Preventive Cognitive Therapy

Rozemarijn S van Kleef et al. BMC Psychiatry.


Background: Major Depressive Disorder (MDD) is a psychiatric disorder with a highly recurrent character, making prevention of relapse an important clinical goal. Preventive Cognitive Therapy (PCT) has been proven effective in preventing relapse, though not for every patient. A better understanding of relapse vulnerability and working mechanisms of preventive treatment may inform effective personalized intervention strategies. Neurocognitive models of MDD suggest that abnormalities in prefrontal control over limbic emotion-processing areas during emotional processing and regulation are important in understanding relapse vulnerability. Whether changes in these neurocognitive abnormalities are induced by PCT and thus play an important role in mediating the risk for recurrent depression, is currently unclear. In the Neurocognitive Working Mechanisms of the Prevention of Relapse In Depression (NEWPRIDE) study, we aim to 1) study neurocognitive factors underpinning the vulnerability for relapse, 2) understand the neurocognitive working mechanisms of PCT, 3) predict longitudinal treatment effects based on pre-treatment neurocognitive characteristics, and 4) validate the pupil dilation response as a marker for prefrontal activity, reflecting emotion regulation capacity and therapy success.

Methods: In this randomized controlled trial, 75 remitted recurrent MDD (rrMDD) patients will be included. Detailed clinical and cognitive measurements, fMRI scanning and pupillometry will be performed at baseline and three-month follow-up. In the interval, 50 rrMDD patients will be randomized to eight sessions of PCT and 25 rrMDD patients to a waiting list. At baseline, 25 healthy control participants will be additionally included to objectify cross-sectional residual neurocognitive abnormalities in rrMDD. After 18 months, clinical assessments of relapse status are performed to investigate which therapy induced changes predict relapse in the 50 patients allocated to PCT.

Discussion: The present trial is the first to study the neurocognitive vulnerability factors underlying relapse and mediating relapse prevention, their value for predicting PCT success and whether pupil dilation acts as a valuable marker in this regard. Ultimately, a deeper understanding of relapse prevention could contribute to the development of better targeted preventive interventions.

Trial registration: Trial registration: Netherlands Trial Register, August 18, 2015, trial number NL5219.

Keywords: Functional neuroimaging; Major depressive disorder; Neurocognitive mechanisms; Prevention; Randomized controlled trial; Recurrence; Remission; Therapy prediction.

Conflict of interest statement

The authors declare that they have no competing interests.


Fig. 1
Fig. 1
Flowchart providing an overview of the NEWPRIDE study design

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