Biological psychiatry global open science · 2026
Neurocognitive Mechanisms of Preventive Cognitive Therapy as Relapse Prevention in Remitted Major Depressive Disorder: A Randomized Controlled Trial.
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van Tol Marie-José, van Kleef Rozemarijn, Eike Ronja, van Valen Evelien, Marsman Jan-Bernard, Renken Remco, Aleman André, Bockting Claudi
Аннотация
BACKGROUND: Major depressive disorder (MDD) is a highly recurrent psychiatric disorder. Understanding mechanisms of effective treatments that lower recurrence risk provides an opportunity to identify neurocognitive targets for recurrence prevention. Here we studied neurocognitive mechanisms of preventive cognitive therapy (PCT).
METHODS: Fifty medication-free individuals who were remitted from MDD and at high risk for recurrence were randomized to 8 sessions of protocolized PCT or a waiting list control (WLC) group as part of the NEWPRIDE (Neurocognitive Working Mechanisms of the Prevention of Relapse in Depression) study (NTR5368). Individuals were assessed at baseline and a 3-month follow-up using functional magnetic resonance imaging, cognitive testing, and clinical questionnaires. Primary outcomes were changes in 1) prefrontal cortex activation during effortful emotion regulation and 2) biased automatic processing, covering positive and negative affective dimensions. Secondary outcomes included changes in symptomatology, cognitive and affective reactivity, and emotion regulation styles. Linear mixed models and repeated-measures analyses of variance were conducted to test for PCT-induced changes.
RESULTS: Following PCT (vs. WLC), decreased (dorso)medial prefrontal activation during effortful regulation of positive affect and decreased pregenual anterior cingulate activation during effortful regulation of positive and negative affect were observed, alongside increased reactivity of positive self-related thinking and lower negative affect responsivity.
CONCLUSIONS: Results from this primary analysis show that PCT, which is a nonpharmacological preventive intervention, has neuromodulatory effects on the prefrontal brain circuitry that underpin the regulation of affect and boost positive thinking about oneself, which is associated with lower negative affect. Training the affect and beliefs to more positive content may strengthen the neural circuitry that is implicated in guarding against the activation of negative affect and beliefs in the face of daily negative events, thereby lowering the risk for recurrence.
METHODS: Fifty medication-free individuals who were remitted from MDD and at high risk for recurrence were randomized to 8 sessions of protocolized PCT or a waiting list control (WLC) group as part of the NEWPRIDE (Neurocognitive Working Mechanisms of the Prevention of Relapse in Depression) study (NTR5368). Individuals were assessed at baseline and a 3-month follow-up using functional magnetic resonance imaging, cognitive testing, and clinical questionnaires. Primary outcomes were changes in 1) prefrontal cortex activation during effortful emotion regulation and 2) biased automatic processing, covering positive and negative affective dimensions. Secondary outcomes included changes in symptomatology, cognitive and affective reactivity, and emotion regulation styles. Linear mixed models and repeated-measures analyses of variance were conducted to test for PCT-induced changes.
RESULTS: Following PCT (vs. WLC), decreased (dorso)medial prefrontal activation during effortful regulation of positive affect and decreased pregenual anterior cingulate activation during effortful regulation of positive and negative affect were observed, alongside increased reactivity of positive self-related thinking and lower negative affect responsivity.
CONCLUSIONS: Results from this primary analysis show that PCT, which is a nonpharmacological preventive intervention, has neuromodulatory effects on the prefrontal brain circuitry that underpin the regulation of affect and boost positive thinking about oneself, which is associated with lower negative affect. Training the affect and beliefs to more positive content may strengthen the neural circuitry that is implicated in guarding against the activation of negative affect and beliefs in the face of daily negative events, thereby lowering the risk for recurrence.