The Use of Behavioral Reconsolidation Interference in Depressive Disorders. A Double‐Blinded Randomized Controlled Experimental Registered Report

TL;DR

This study explores whether reconsolidation interference can reduce recurrence in depression-like states, but finds no strong evidence for its effectiveness.

Contribution

The first experimental test of reconsolidation interference for depression-like helplessness.

Findings

No robust group differences were found between interventions on behavioral, self-report, or EEG measures.

Exploratory analysis suggests brain-derived neurotrophic factor (BDNF) may mediate outcomes.

The study confirms successful induction of helplessness but not its modification via reconsolidation.

Abstract

Depressive disorders often show recurrent courses that cannot be sufficiently prevented by existing therapeutic protocols. In other affective disorders, recurrence has been linked to three mechanisms –spontaneous recovery, accelerated new/relearning, and reinstatement– which are related to the preservation of disorder‐related memory traces even through successful extinction‐based interventions. Reconsolidation‐interference protocols aim to directly alter such traces by reactivating and destabilizing them before intervention. While this approach has shown benefits in fear, craving, and trauma‐related symptoms, its application to depression remains untested. To our knowledge, this study provides the first experimental evidence of its utility in depression‐like states. Sixty participants took part in a three‐day, three‐group, double‐blind randomized controlled trial. On day one, helplessness was induced using a modified unsolvable anagram task. On day two, participants were randomized into three groups undergoing different interventions while completing another cognitive demanding task: (1) extinction, where participants experienced success from start to finish; (2) reconsolidation, where participants briefly reexperienced failure before succeeding; or (3) reactivation, where failure repeated. On day three, the helplessness task was presented again to evaluate susceptibility for recurrence across conditions. Behavioral, self‐report, and EEG data were collected. Across test days, participants showed reduced motivation and performance, attributing failure to personal ability, confirming successful helplessness induction. However, interventions at day two produced no robust group differences on behavioral, self‐report, or EEG measures. Exploratory analyses suggested that brain‐derived neurotrophic factor (BDNF) levels may have mediated outcomes. Findings do not confirm reconsolidation‐based behavioral interference as effective for depression‐like helplessness. Nonetheless, exploratory results highlight BDNF as a potential mediator, warranting further study on its role in postretrieval extinction effects in depression.

Recurrence rates in depressive disorders remain high even after successful therapy. This study proposes an experimental protocol that assesses the possibility of targeted memory reconsolidation to modify long‐lasting vulnerability. The findings of this study provide first evidence concerning the potential and difficulties regarding applicability of this approach in the context of depression thereby paving the way for the translation of basic scientific results toward clinical application.

Figures